It has recently been shown by Chang et al. (J Immunol 2000; 165:3584-91) that the maturation of dendritic cells (DC) in the presence of long-chain fatty acids redirects DC into Th0-Th2-inducing cells suggesting the involvement of a receptor for long-chain fatty acids like members of the peroxisome proliferator-activated receptors (PPAR) superfamily. Here, we show that immature and mature monocyte-derived DC (Mo-DC) express PPAR alpha , PPAR delta , PPAR gamma 1 and PPAR gamma 2 mRNA with the highest level of PPAR gamma 1 mRNA. We were only able to observe the expression of PPAR gamma 1 protein by Western blotting probably because the protein level of the other subtypes is below the detection limit. Synthetic ligands specific for PPAR alpha , PPAR delta or PPAR gamma added at day 0-6 have similar effect on the maturation of Mo-DC driving the maturation of Mo-DC with atypical phenotype, reduced expression of IL-10, IL-12 p35 and IL-12 p40 mRNA and with reduced stimulatory effects in mixed leucocyte reaction (MLR). Our data suggest that naturally occurring PPAR ligands like fatty acids and fatty acid derivates have anti-inflammatory effects by redirecting DC into a less stimulatory mode.