IL-5 is essential for granuloma eosinophilia in mice infection with schistosomiasis. The granulomas constitutively make IL-5 that originates from granuloma CD4+ T lymphocytes. This observation prompted us to learn whether non-T cell elements in the granuloma can promote constitutive IL-5 production. Neither granuloma eosinophils nor spleen cells from infected mice constitutively produced detectable levels of IL-5. Yet, mixing spleen cells with granuloma eosinophils resulted in spontaneous IL-5 secretion without promoting IL-4 production. Moreover, the admixed cultures were more responsive to anti-CD3 or soluble egg Ag than were cultures containing spleen cells alone. IL-5 ELISPOT assays in Transwell chambers showed that the cellular origin of IL-5 in the admixed cultures was the spleen cells, and that the phenomenon did not require cell-to-cell contact with granuloma eosinophils. Also, admixed cultures of granuloma eosinophils and spleen cells released less IL-5 in the presence of mAb that specifically blocked the biologic activity of either IL-2, IL-2R, or IAk. However, adding rIL-2 to spleen cell cultures at concentrations up to 100 U/ml could not stimulate secretion of IL-5. Because eosinophil supernatants contained no IL-2 as assessed by CTLL-2 bioassay, the release of IL-5 in response to eosinophils was not likely secondary to eosinophil secretion of IL-2. Thus, it appears that eosinophils produce a soluble substance that, with IL-2 and ongoing class II MHC/TCR interaction, enhances lymphocyte IL-5 output.