The parasite-parasite interaction of Salmonella and Schistosoma was studied. Salmonella typhimurium LT2 was found to associate in vitro with three human species of Schistosoma: Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum. Genetic mutants of S. typhimurium were allowed to interact with ligatured and unligatured worms of S. mansoni in vitro. These studies were undertaken to elucidate the mechanism(s) of the parasite-parasite interaction of Salmonella on the surface of Schistosoma. The ga/E and fla mutants showed 100% association with male schistosomes, but a reduced interaction with female worms. The rough A and pili mutants showed a significant reduction in the ability to associate with both male and female S. mansoni. Observations with the scanning electron microscope revealed that pili function in adhesion of Salmonella to the surface tegument of S. mansoni and S. haematobium. The association of Salmonella and Schistosoma may contribute to persistence of salmonella infection.