There is a recent report of low efficacy of praziquantel (PZQ) treatment of human schistosomiasis in a new Schistosoma mansoni focus in northern Senegal. Biomphalaria pfeifferi snails with patent infections were collected from the area of the focus and transported to the United Kingdom. Groups of mice were infected with cercariae from this Senegalese isolate, or with laboratory-maintained Kenyan or Puerto Rican isolates. In two separate experiments, PZQ was less effective against the parasite from Senegal than against the two other geographic isolates. The reduced susceptibility of S. mansoni to PZQ in infected human populations has important implications for current schistosomiasis control programs.