Mice infected with Schistosoma mansoni at day 0 were given cyclosporin A (Cy-A) from day 1 to day 3 and reinfected at day 45. They were perfused to recover worms at day 66, at which time mature and immature worms, established from infection and reinfection, respectively, could easily be distinguished. A high degree of protection (90–100%) was obtained against both primary and secondary infection. Elimination of the parasites was an early event since only 10–30% of schistosomula, as compared to those in control mice, were recovered at day 6 by pulmonary perfusion. Our data indicate that a direct effect of Cy-A cannot be demonstrated. Nevertheless, Cy-A did evoke a high level of protection against schistosome infection.