Clusterin, a multifunctional glycoprotein, characterized as a potent inhibitor of the membrane attack complex of complement, is also known to be the product of a gene that is highly up-regulated in certain tissues undergoing programmed cell death. We have studied the expression of this gene in the rat thymus after the induction of thymocyte programmed cell death (PCD) by in vivo dexamethasone administration. Northern blot analysis of clusterin mRNA 2, 4, 6 and 8 hr after dexamethasone administration in a total of 21 rats revealed no modification in the level of clusterin gene expression. In situ hybridization demonstrated that clusterin gene expression is macroscopically confined to the medullary region of the thymus, and that this distribution is not modified by dexamethasone administration. These results strongly suggest that in the rat, clusterin gene expression is not associated with the programmed cell death of thymocytes following in vivo dexamethasone administration. In situ hybridization of the clusterin cRNA to thymus cryostat sections confirmed the results obtained by Northern blot analysis. Indeed, no consistent increase in the amount of clusterin mRNA was detectable at any of the time-points studied. The macroscopic distribution of clusterin mRNA in the rat thymus was identical to that previously observed in the human thymus, clusterin message being essentially detected within the medullary regions. No modification in the macroscopic distribution of clusterin gene expression was detected after dexamethasone administration. These results suggest that, like the human thymus, medullary epithelial cells are the site of clusterin gene expression in the rat thymus. Moreover they indicate that an increase in the extent of ongoing thymocyte PCD does not significantly modify the rate or site of clusterin gene expression within the thymus.