Eosinophil stimulation promoter (ESP) is a lymphokine activity that stimulates eosinophil migration and is produced by mitogen or specific Ag stimulation of spleen cells from mice infected with Schistosoma mansoni. It is also produced by intact, schistosome egg-induced granulomas isolated from the livers of such mice without additional antigenic exposure. The production of ESP activity is decreased during chronic infection in a time course coordinate with granuloma modulation. Characterization of ESP was pursued to determine its relationship to other cytokines and to identify factors that may play a role in granuloma formation and modulation. Chromatographic separations, assays of recombinant cytokines, and cytokine-specific immunodepletions were used in the characterization. ESP+ supernatant fluids contain both granulocyte-macrophage CSF and IL-5. The removal of both granulocyte-macrophage CSF and IL-5 is required to eliminate ESP activity, and together they act synergistically to constitute ESP.