The effect of the new schistosomicide praziquantel (2-cyclohexyl-carbonyl-1,2,3,6,7,11 b-hexahydro-2H-pyrazino[2,1a]isoquinolin-4-one) on the miracidia and cercariae of Schistosoma mansoni was investigated. In vivo praziquantel inhibits hatching of miracidia for 24 h after administration of 500 mg/kg to infected mice. In vitro a concentration of 10 microgram/ml inhibits subsequent hatching in drug-free water. Free swimming miracidia are rapidly killed by 1 microgram/ml. Even 0.01 microgram/ml is still partially effective. In a solution of 0.03 microgram/ml cercariae lose their ability to swim within 10 min. This effect is reversible in drug-free water. Morphological damage to cercariae incubated in 0.1 microgram/ml is clearly evident. However, cercariae are fully infective when given subcutaneously to mice after a 3-h incubation period. Incubation in 1 microgram/ml reduces the infection rate by 80%. A 2-h incubation in 0.1 microgram/ml almost completely inhibits the percutaneous infection through the abdominal skin. The number of cercariae that develop to schistosomules is reduced by more than 90%. After a 2-h incubation in a concentration of 0.01 microgram/ml the swimming ability of cercariae is impaired in such a way that the number of cercariae penetrating in the tail immersion test and developing to schistosomules is reduced by half. Praziquantel is a more potent protective agent than the molluscicides copper sulphate, sodium pentachlorophenate and Bayluscide or cadmium and zinc ions.