Cyclosporin A (CsA), administered subcutaneously as 5 daily injections of 50 mg·kg−1, reduced the numbers of Schistosoma mansoni perfused from MF1 mice at 7 weeks post-infection. The timing of drug administration revealed that the antischistosomal effects were greater when CsA treatment coincided with or was within a few days of infection with a parasite. CsA exerted a clear prophylactic effect, which decreased with time and was virtually abolished by 4 months pre-infection. Adult worms treated in vivo were partially susceptible to CsA. In addition to its antiparasite action, CsA reduced hepatosplenomegaly due to schistosomiasis and diminished the granulomatous inflammatory response of mice to parasite eggs in the liver. The mode of action of CsA is not understood but evidence is presented that supports the proposition that the anti-parasite effects are perhaps host-mediated.