Cytokines control many of the steps in the complex pathways of immune and inflammatory responses in mammals. Recent reports also indicate that some invertebrates may produce cytokines such as interleukin 1 (IL-1). Certain strains of the snail, Biomphalaria glabrata (intermediate host for the human blood fluke, Schistosoma mansoni), possess a soluble plasma factor that stimulates the haemocyte-mediated killing of larval schistosomes, making them resistant to infection. In this study, we have sought to determine whether these snails possessed IL-1 in their plasma, and whether this cytokine was associated with resistance of B. glabrata to S. mansoni. Plasma from susceptible (M-line) and resistant (10-R2, 13-16-R1) strains of B. glabrata that had been unexposed or exposed to S. mansoni were tested for the presence of IL-1-like activity. Experiments employing both a bioassay and an immunoassay indicated that an IL-1-like molecule was present, in varying quantities, among the snail strains. Further, plasma IL-1 levels were significantly affected by exposure to S. mansoni, with levels dropping in M-line and 10-R2 snails, but increasing in the 13-16-R1 strain. However, both resistant strains maintained significantly higher IL-1 levels than M-line snails. Recombinant, human IL-1 (rhIL-1) was shown to prime haemocytes from both resistant snail strains for superoxide production, but had no effect on haemocytes from susceptible B. glabrata. Moreover, the addition of an IL-1 receptor antagonist protein (IRAP) eliminated this priming effect. Priming with rhIL-1 and/or IRAP had no effect on phagocytosis rates in any of the snail strains tested. These findings suggest that IL-1 plays a significant role in the ability of B. glabrata to resist infection by S. mansoni. To our knowledge, this is the first study to show that a cytokine is associated with the immunological response of an invertebrate to a pathogen. © 1994.