The schistosomicidal efficacy of praziquantel (2 x 500 mg/kg), oxamniquine (1 x 100 mg/kg) and combined one-third the curative dose of each of them (333 mg/kg praziquantel + 33 mg/kg oxamniquine), were correlated to gonadal steroid hormonal changes and state of disease immunopathology, in mice infected with 100 Schistosoma mansoni (S. mansoni) cercariae. Maximum efficacy recorded with combination regimen particularly 4 weeks after treatment, was accompanied by maximum reduction in granuloma volume (65%), least fall in testosterone level (-56.2 and -60.2% in male and female mice respectively) and increased progesterone level (+33.9 and +81.5% in male and female mice respectively). These findings revealed a potentiated effect of combination therapy on mature infection and the possible involvement of gonadal steroid hormones in affecting the efficacy of schistosomicidal drugs and state of disease immunopathology.