As a boy in the 1980s James Wexler, an engineer in Boston, spent his summers covered in furious, itchy welts. Every July his parents sent him to Camp Becket in the Berkshires, a boys-in-the-woods kind of place with musty cabins and no electricity. Despite applying thick coats of DEET-based Off! repellent, Wexler always returned from his month in western Massachusetts with dozens of mosquito bites and what felt like a pint less blood.

"Other kids could go without repellent and the mosquitoes wouldn't touch them," says Wexler, now 27. "I think they just like me more."

Many share Wexler's frustration at the inadequate protection afforded by insect repellents, including DEET, which is generally regarded as the best that science currently has to offer. Improving on its performance might hinge in part on understanding what lies behind the truth of his observation: not everyone attracts mosquitoes equally.

DEET: The One to Beat
DEET (chemical compounds more formally known as both N,N-diethyl-meta-toluamide and N,N-diethyl-3-methylbenzamide)—first developed by the U.S. Department of Agriculture (USDA) in 1946 and patented for use in jungle warfare by the U.S. Army—does keep bugs from biting. One study published in The New England Journal of Medicine in July 2002 found that a 23.8 percent DEET solution deterred caged mosquitoes from biting the arms of human volunteers for 302 minutes on average, compared with 20 minutes for the old standard, citronella.

Similarly, 2005 comparisons by the Australian consumer group CHOICE found that formulations of DEET and another synthetic repellent called picaridin both outperformed and outlasted citronella and other natural compounds.

Yet even the best repellents do not work well for everyone. Why not?

Varying Effectiveness
First, insects respond to certain attractants: lactic acid on the skin produced by muscular activity, exhaled carbon dioxide, high body temperature, moisture and even skin color (they prefer darker shades). Your diet, exercise, environment and skin pH all influence how tasty you seem to pests—and how hard repellents must work to keep them away.

Second, in addition to mosquitoes, the army of biting insects includes diverse battalions: ticks, blood-feeding mites, deerflies, horseflies, blackflies, biting midges, fleas and lice, to name just a few. DEET dispels mosquitoes but only protects somewhat against biting mites and ticks, and not at all against horseflies, deerflies or biting midges.

Precisely how DEET works is still unclear, despite decades of study. The most longstanding theory has been that DEET jams mosquitoes' ability to smell lactic acid, in effect leaving them blind to the presence of nearby sources of blood. But a 2008 study in the Proceedings of the National Academy of Sciences by Zainulabeuddin Syed and Walter Leal of the University of California, Davis, suggested that something about DEET might instead actively repel mosquitoes.

Toxicity Issues
Even if DEET were 100 percent effective in chasing away mosquitoes, however, its toxicity would still be a drawback. DEET is generally safe, notes Emily Zielinski-Gutierrez, a behavioral scientist at the U.S. Centers for Disease Control, but it can sometimes cause rashes or irritation, or even seizures and death if ingested. So "anything you can do to limit a child's exposure is good," says Dave Stone, director of the National Pesticide Information Center.

DEET-based repellents should therefore not be treated like sunscreen that can be lathered on generously and frequently. With all pesticides you should avoid covering the hands or face. If a DEET formula claims to protect for eight hours, don't apply it every two hours just because you go swimming or to "bolster your defenses".

Developing Safer Alternatives
For all those reasons, scientists are looking for safer, more enduring, more effective alternatives to DEET. At North Carolina State University in Raleigh, for example, entomologist Michael Roe is developing a compound based on a chemical called 2-undecanone, found in tomato plants, that rivals DEET in efficacy and has so far shown no negative health risks.

Other researchers have used computer models to identify at least 24 synthetic chemical compounds that should repel insects; Ulrich Bernier, a research chemist at the USDA's Mosquito and Fly Research Unit, has tested them all. Twenty performed as long—or as much as three times as long—as DEET in tests on cloth, although their safety has not been established. Tests with caged mosquitoes and treated human arms are up next, along with a battery of studies to determine safety, efficacy on various insects and other variables.

Notwithstanding progress in developing newer, better insect repellents, however, one further complication may always leave some people less satisfied with them. Because the swelling and itching around a bite is essentially an allergic reaction to a mosquito's saliva, one person may show many more welts than another in response to the same number of bites. For mosquito bait like Wexler, staying indoors may always be the best solution.