Praziquantel (PQ), a tetrahydroquinoline derivative, is a new and clinically effective antischistosomal drug, which has been shown to lack or to possess very weak mutagenic activity. However, in bacteria, this compound can act as a weak comutagen that increases the mutagenicity of several chemical mutagens and carcinogens. We have found that PQ can act as a very weak comutagen in animal cells. At 10 to 50 micrograms/ml, PQ increased the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine and 2-methoxy-6-chloro-9-[3-(2-chloroethyl)amino-propylamino]acridine dihydrochloride about 2-fold in Chinese hamster V-79 cells. In C3H/10T 1/2 mouse embryo cells, PQ exhibited only negligible comutagenic activity. PQ did not oncogenically transform C3H/10T 1/2 cells but had a pronounced effect on 3-methylcholanthrene-induced transformation of these cells. When PQ was coadministered with or added after 3-methylcholanthrene treatment, the number of type III foci produced was about 5-fold lower than in cultures treated with 3-methylcholanthrene alone. Therefore, PQ can inhibit type III focus formation in C3H/10T 1/2 cells.