Praziquantel is a broad spectrum anti-helminthic drug active against a variety of parasitic trematodes and cestodes. This report studies the effects of a schistosomacidal regimen of praziquantel on the generation of the cell-mediated and humoral response capabilities of normal, uninfected mice. Three doses of 100 mg praziquantel/kg body weight at 4-hr intervals cured several strains of mice with Schistosoma mansoni infections of several intensities. When this curative regimen was applied to normal, uninfected mice it did not alter peripheral blood leukocyte counts, circulating eosinophil numbers or splenic weights. Neither did this regimen alter the development of responsiveness to sheep erythrocytes (SRBC) as measured by dermal delayed-type hypersensitivity (DTH) or the number of splenic plaque forming cells. Furthermore, DTH and serum antibody responses to a soluble antigen (bovine serum albumin) were also comparable in treated and untreated mice. It appears that an anti-schistosomacidal regimen of praziquantel does not alter normal murine cellular or humoral immune responses.