The peroxisome proliferator-activated receptor (PPAR)-gamma is a nuclear lipid-activable receptor controlling the expression of genes involved in lipid metabolism and adipocyte differentiation. In order to investigate the possible role of PPAR-gamma in the differentiation of intestinal epithelial cells, we examined its expression in the human colon carcinoma cell line Caco-2, which undergoes rapid cell differentiation in the presence of butyrate. PPARs were quantified on mRNA level by RT competitive multiplex PCR, the corresponding proteins were determined by Western blot. In contrast to PPAR-alpha and PPAR-beta, PPAR-gamma mRNA and protein increased significantly in butyrate-treated Caco-2 cells in a dose- and time-dependent manner. This effect was butyrate-specific, since no change in PPAR-gamma expression could be observed after incubation with propionate or valerate, Activation of PPAR-gamma by ciglitazone further increased butyrate-induced cell differentiation dose-dependently. These data demonstrate a role for PPAR-gamma in the regulation of cell differentiation in Caco-2 cells.