Host immune responses have been shown to enhance the efficacy of several schistosomicidal drugs. The evidence derives mainly from experiments on Schistosoma mansoni infections in the mouse with their immune status variously modulated; this review emphasises praziquantel (PZQ), which is now the main drug used for treatment of human schistosomiasis. Electron microscopy and indirect immunofluorescence indicate that PZQ disrupts the integrity of the surface membranes of S. mansoni, particularly those covering the dorsal tubercles of adult male worms, and this causes antigens which are the targets of antibody attack to be revealed. We review the evidence that two S. mansoni antigens in particular are implicated in the immune-dependent action of PZQ: a 200 kDa glycoprotein and a 27 kDa antigen with non-specific esterase activity. Consistent with the involvement of the latter antigen, increased non-specific esterase activity was demonstrated histochemically on the surface of intact PZQ-treated male worms, and we describe a chromogenic substrate assay for quantifying the amount of esterase activity that is exposed after drug treatment. The potential relevance of these observations for enhancing the efficacy of drugs currently used to treat human schistosomiasis, and for devising novel therapeutic strategies, is discussed.