Praziquantel induces a bilayer to isotropic transition in the absence of Ca2+ in a mixed phospholipid membrane consisting of phosphatidylethanolamine (PE) and phosphatidylserine (PS) at a molar ratio of 2:1 at 25 degrees C or 35 degrees C, irrespective of the lipid/drug molar ratio (10:1; 2:1). Addition of Ca2+ at different PS/Ca2+ molar ratios (4:1, 2:1 or 1:1) leads to a transition to a hexagonal (HII) state. With a phospholipid membrane of different composition (PE/PS molar ratio 4:1) praziquantel exerts quite different effects in the presence of Ca2+ (PS/Ca2+ molar ratio 1:1). An isotropic-signal appears together with a bilayer one at 25 degrees C, while a HII-signal can be detected at 35 degrees C. Thus, two separate phases coexist at this PE/PS molar ratio, while at a PE/PS molar ratio of 2:1, praziquantel and Ca2+ induce only a HII-signal. The results with these model membranes show that praziquantel and Ca2+ exert drastic influences on bilayer-isotropic-hexagonal transitions. The possibility that this drug might act in the schistosomal tegumental membranes in the same way is discussed.