A simplified in vitro technique was utilized to detect cytotoxic antibodies in serum from hosts exposed to cercariae of Schistosoma mansoni. Significant destruction of cultured schistosomules occurred in the presence of immune rat, rabbit, mouse, and monkey serum. Immune sera induced heavy precipitate formation around the schistosomules. The cytotoxic activity resided in the gamma globulin fraction of immune serum and was shown to be almost wholly complement dependent. Immune serum adversely affected the in vivo viability of schistosomules before detection by the dye exclusion technique was possible. Rabbit gamma globulin that exhibited strong in vitro cytotoxicity failed to protect mice against a challenge infection. Serum from rabbits immunized with adult worm culture antigen did not possess significant in vitro cytotoxicity, although this same antigen effectively stimulated resistance in mice to cercarial challenge. These results, coupled with the findings of other investigators, make it difficult to equate the cytotoxic titer of a host's serum with its immune status.