Clusterin, originally isolated as testosterone-repressed prostate message-2 from regressing rat ventral prostate, has been identified with the process of active cell death (ACD). The clusterin gene product is a glycosylated dimer consisting of alpha and beta subunits, resulting from the 70-kilodalton preprotein. To determine its relationship with ACD, we have examined clusterin expression via in situ hybridization and immunohistochemistry. Clusterin message is detected in the supporting cells in both testes and ovaries and the protein surrounds the mature germ cells. The highest level of expression was found in the head region of the epididymis. Clusterin message is also detected in selected cells of uterine glands and ducts both in the normal and pregnant uterus. The expression of clusterin in the developing embryo is most abundant in the choroid plexus, inner ear, and epithelium of the eye. None of the cells in the testes, epididymis, or embryo that express clusterin are undergoing ACD. The expression of clusterin appears to correlate with cell remodelling or differentiation that occurs during these periods of development. However, in the female reproductive system, we found clusterin to be expressed in both differentiating as well as dying cells. These results suggest that clusterin may provide support for cells undergoing specific biochemical and (or) physical changes. Our results are consistent with the hypothesis that clusterin is an antiinflammatory agent.