Praziquantel is the drug of choice for schistosomiasis chemotherapy. Although the exact mechanism of how praziquantel kills schistosomes remains poorly understood, the immune response of the host is an important factor in drug efficacy. It is thus possible that disease states of humans that lead to immunodeficiencies, such as infection with human immunodeficiency virus-1 (HIV-1), may render praziquantel less effective in treating schistosomiasis. To test this hypothesis, persons with high levels of Schistosoma mansoni infection who were or were not also infected with HIV-1 were treated with a standard regimen of praziquantel and monitored by quantitative fecal examination and plasma circulating cathodic antigen. Both groups responded to praziquantel therapy equally and individuals with low percentages (< 20%) of CD4+ T cells did not differ from individuals with higher CD4 cell percentages. These data demonstrate that persons with HIV-1 infection can be treated effectively for schistosomiasis with praziquantel.