UV-irradiated and gamma-irradiated schistosomula of Schistosoma mansoni induce high levels of resistance to challenge infection in experimental hosts. It was observed that both types of irradiation severely inhibited protein synthesis by the parasite larvae. Schistosomula were treated with the metabolic inhibitor actinomycin D to simulate this effect of irradiation. The ability of these drug-treated larvae to induce immunity was tested in animal protection experiments. Our results suggest that inhibition of protein synthesis may help to generate the enhanced immunogenicity of irradiated schistosomula. In explanation, we propose that irradiated schistosomula may be such potent immunogens because they express antigens in disrupted, abnormal conformations. Inhibition of protein synthesis may both directly create such modified antigens, and also ensure that they persist and accumulate for presentation to the host immune system.