Lymphokine mRNA for IL-2, IL-4, IL-5, IL-10, and IFN-gamma was identified in total RNA, extracted from granuloma and spleen cells of Schistosoma mansoni-infected mice. The specific mRNA in these preparations was identified after reverse transcription and polymerase chain reaction amplification. In some experiments, spleen cells were incubated in the presence of soluble egg antigens or mitogen before RNA extraction. Also, the secretion of these lymphokines from cells maintained in vitro was measured by ELISA or bioassay. The spleen cells from either uninfected or infected mice constitutively released no detectable cytokines and expressed only IL-10 mRNA prominently. Mitogen induced spleen cells from either source to express IL-2 and IFN-gamma mRNAs and their corresponding proteins. Also, spleen cells from noninfected mice stimulated with mitogen expressed IL-4 mRNA, but not IL-5 mRNA, and no detectable protein products. Yet, IL-5 was inducible in spleen cells from infected animals. Soluble egg antigens induced spleen cells from infected mice to prominently express a variety of cytokine genes and produced large amounts of cytokine proteins, but spleen cells from uninfected mice did not respond. Unlike the spleen, the granulomas constitutively expressed mRNAs for all the cytokines examined. Yet, there was limited expression of IL-2 mRNA as compared to that of other cytokines. Except for IL-5, unfractionated granuloma cells constitutively released cytokines at low or undetectable levels. Soluble egg antigens or mitogen enhanced the production of all cytokines to different extents. These observations indicate that schistosome granulomas and spleens express both Th1 and Th2 cytokines. The various lymphokines display complex differences in both lymphokine mRNA and product expression. These results suggest that the production of granuloma lymphokines is governed selectively, possibly by a variety of undetermined regulatory pathways.