Single oral doses of amoscanate (4-isothiocyanato-4′-nitrodiphenylamine), an experimental antiparasitic agent, are highly effective in animals against the four major species of schistosomes which infect humans. Two prospective, randomized, double blinded, placebo controlled Phase I studies were designed to evaluate the tolerance and safety of the 5% aqueous suspension of 2-µ particles of amoscanate administered to healthy male volunteers. In addition to routine safety monitoring, particular attention was directed toward detecting hepatic, neurological, cardiovascular or ocular toxicity. Three of four men who received 3.5 mg/kg of amoscanate developed mild, reversible hepatotoxicity, which could not be unequivocably attributed to the drug. In the second study, of 1 mg/kg amoscanate, there was no statistically significant evidence of hepatotoxicity, although 1 of 12 drug recipients developed transient liver chemistry changes. Despite intensive monitoring, there was no evidence in either study of significant symptomatic complaints, or of neurological, cardiovascular or ocular toxicity. No mutagenic activity attributable to amoscanate was detectable in the urine. These results suggest that this formulation of amoscanate, at 1 mg/kg, is sufficiently well tolerated and safe to justify evaluation for efficacy in patients with schistosomiasis.