IL-11, derived from a bone marrow stromal cell line, has pleiotropic effects on both hematopoietic cells and nonhematopoietic cells. However, no previous studies have systematically addressed expression of IL-11 in primary tissues in vivo and the relationship of IL-11 tissue specific gene expression and function of IL-11 is not clear. In the present study, we examined constitutive IL-11 expression in various murine adult tissues in vivo. IL-11 mRNA is expressed in a wide range of normal tissues (including hematopoietic organs) at levels only detected by RT-PCR. IL-11 protein was detected in brain and testis by Western blot analysis. The in vivo cellular distribution of IL-11 expression was examined by in situ hybridization. In brain, IL-11 message is distributed in granular layer dentate gyrus and pyramidal cell layers of hippocampus. IL-11 is also expressed in anterior horn cells and lateral column neuronal cells of the spinal cord. In testis, IL-11 mRNA is expressed in round spermatids at stage VI-IX seminiferous tubules. IL-11 expression in testis is restricted to developing spermatogonia and is developmentally regulated, since no expression is seen in mice genetically deficient in germ cells and in mice prior to sexual maturation. These expression data correlate with functional data demonstrating that IL-11 stimulates proliferation in vitro of a hippocampus neuronal progenitor cell line and administration of IL-11 in vivo accelerates recovery of spermatogenesis after cytotoxic therapy. These studies suggest that IL-11 may be an important regulator in neural and testicular function.