The effects of 3-methylcholanthrene, butylated hydroxyanisole, and phenobarbital on the expression of glutathione S-transferase (GST, EC 2.5.1.18) were examined in the human parasite Schistosoma mansoni. GST specific activity toward 1-chloro-2,4-dinitrobenzene increased by 170% in parasites recovered from mice injected with 3-methylcholanthrene and 230% in parasites recovered from mice maintained on a diet containing butylated hydroxyanisole. These increases in specific enzyme activity were paralleled by accumulation of mRNA hybridizing to pGT16.4, a cDNA clone that encodes the most abundant GST subunit, SmGST-3. Northern hybridization analysis showed a 5-fold increase in mRNA hybridizing to pGT16.4 72 h after exposure to 3-methylcholanthrene, a 10-fold increase after 12 days exposure to butylated hydroxyanisole, and a 6-fold increase 16 h after treatment with phenobarbital. In contrast, no accumulation of mRNA hybridizing to either of two other cDNA clones that encode the SmGST-4 and SmGST-6 subunits was detected. Hybrid select translation using pGT16.4 combined with reverse-phase high-pressure liquid chromatographic analysis demonstrated that in addition to SmGST-3 mRNA, the clone also hybridized to mRNA species encoding the SmGST-1 subunit, a member of the same isoenzyme family. High-pressure liquid chromatographic analysis of GST affinity purified from butylated hydroxyanisole-exposed parasites revealed a 2.5-fold increase in the concentration of SmGST-1 and SmGST-3 present compared with an equivalent amount of tissue from control organisms. There was no change, however, in the SmGST-1 to SmGST-3 ratio (1:6), indicating that both subunits were induced to the same extent by this agent. The results of these studies suggest that alterations in GST expression may influence the parasite's survival within the host environment.