1. The mutagenicity of serum and urine from guinea pigs treated with a single oral dose (500 mg/kg) of benznidazole and nifurtimox was assayed using the Salmonella/plate incorporation test with strain TA 100 and a nitroreductase-deficient derivative, TA 100NR. 2. The urine and blood of animals treated with nifurtimox were not mutagenic for either tester strain. 3. The urine and blood of animals receiving benznidazole were mutagenic to the TA 100 but not to the TA 100NR strain. Similar results were obtained with nitrofurantoin-treated animals. Maximum mutagenicity values were obtained in serum and urine of treated animals 90 min and 24 h after administration, respectively. 4. Mutagenicity induced by benznidazole in the serum and urine of treated animals was not altered when assayed in anaerobic environments. 5. These results indicate that benznidazole and nifurtimox are not metabolized by the mammalian host into stable mutagenic derivatives detectable by the Ames test. Based on these data, we suggest that the potential cancer risk to patients treated with these drugs is small but should be further evaluated.