Plasmodium falciparumandTrypanosoma cruziwere killed by two novel lytic peptides (SB‐37 and Shiva‐1) in vitro. Human erythrocytes infected withP. falciparum, and Vero cells infected withT. cruzi, were exposed to these peptides. The result, in both cases, was a significant decrease in the level of parasite infection. Furthermore, the peptides had a marked cytocidal effect on trypomastigote stages ofT cruziin media, whereas host eukaryotic cells were unaffected by the treatments. In view of the worldwide prevalence of these protozoan diseases and the lack of completely suitable treatments, lytic peptides may provide new and unique chemother‐apeutic agents for the treatment of these infections.—Jaynes, J. M.; Burton, C. A.; Barr, S. B.; Jeffers, G. W.; Julian, G. R.; White, K. L.; Enright, F. M.; Klei, T. R.; Laine, R. A. In vitro cytocidal effect of novel lytic peptides onPlasmodium falciparumandTrypanosoma cruzi. FASEB J.2: 2878‐2883; 1988.