In vitro growth of the protozoan parasite Giardia lamblia was highly sensitive to certain anthelmintic benzimidazoles. Albendazole and mebendazole were 30- to 50-fold more active than metronidazole and 4- to 40-fold more active than quinacrine. Thiabendazole, a noncarbamate benzimidazole, was less active. Since lack of intestinal absorption makes mebendazole an attractive new antigiardial agent, its in vitro activity was further characterized. At low concentrations (0.05 micrograms/ml) mebendazole had a static effect on G. lamblia growth; however, lethal activity was observed at a concentration fivefold lower (0.3 micrograms/ml) than necessary for the cidal agent metronidazole. Two observations are consistent with a microtubule target for mebendazole. First, attachment of cells to the culture tube, mediated by the ventral disk and flagella, was rapidly disrupted by mebendazole treatment. Second, the characteristic cell structure was grossly distorted by treatment. No mebendazole-resistant G. lamblia were detected in a population of 10(8) cells.