Schistosomula were recovered from the skin of mice following primary infections. On the surface of such "infecting schistosomula", mouse C3 could not be detected by immunofluorescence. Subsequent incubation in vitro with fresh mouse serum led to the effective deposition of mouse C3 on schistosomula only when they were recovered within a few hours but not after one or two days following infection. In vitro deposited murine C3c was lost from i.v. injected schistosomula in the mouse circulation within one day as was human C3c. Infecting schistosomula exhibited a close to complete resistance to the lytic in vitro activity of human complement. This resistance was complete in older parasites. It existed in spite of the presence of parasite-bound human C9, which was detectable on all developmental stages of schistosomes following incubation in fresh, but not inactivated human serum. Lung schistosomula, 3-week and 6-week-old schistosomes were resistant to cellular cytotoxicity upon incubation with fresh human serum and rat peritoneal exudate cells although cell adherence mediated by human C3b was demonstrated with lung worms. The data suggest that schistosomula may evade in vivo the lytic activity of complement and also complement-mediated cellular cytotoxicity. Depending on the species of serum, this can be demonstrated in vitro by lack of opsonization or by resistance to lytic and cellular attack mechanisms.