BACKGROUND: Several studies have shown an inverse association between helminth infections and atopy, but none have clearly established that the pathogens themselves, rather than other associated factors, cause the suppression of atopy. To show a direct link, prospective intervention studies are required. METHODS: A randomized, controlled trial was performed to study whether repeated anthelminthic treatment results in increased allergic sensitivity to house dust mites (HDMs) in chronically infected children. The trial population consisted of 317 Gabonese schoolchildren with a high prevalence of intestinal helminths. Intervention consisted of treatment every 3 months with praziquantel and mebendazole and with placebo in the control group. Follow-up lasted 30 months: at 6-month intervals, skin-test sensitivity to mites, helminth infection status, and levels of total IgE were determined. RESULTS: Treatment resulted in a significant increase in the rate of developing skin sensitivity to HDMs (hazard ratio, 2.51; 95% confidence interval, 1.85-3.41), which was mediated, in part, by reductions in Ascaris and/or Trichuris infections. Levels of total IgE were reduced, but this did not mediate the effect of treatment on skin-test reactivity. CONCLUSIONS: Anthelminthic treatment of chronically infected children results in increased atopic reactivity, which indicates that helminths directly suppress allergic reactions.