Rodent brown adipocytes express peroxisome proliferator activated receptor-α (PPARα) and PPARγ and while the rodent uncoupling protein-1 (UCP-1) gene contains a putative peroxisome proliferator response element (PPRE), only PPARγ activation by thiazolidinediones increase UCP-1 mRNA levels. We have investigated this phenomenon in foetal rat brown adipocytes (FBA) and show that although transactivation occurs in FBA containing a plasmid encoding 4.5kb of the 5'-flanking region of the rat UCP-1 promoter ((-4551)-UCP-1-CAT) treated with either the selective PPARγ agonist rosiglitazone (1.0 μM) or the selective PPARα agonist Wy 14643 (10.0 μM), only rosiglitazone induced transcription of UCP-1 mRNA. Furthermore, Wy 14643 (10 and 100.0 μM) abolished rosiglitazone-induced UCP-1 mRNA induction in spite of a transactivation event occurring with the combination treatment. Thus in FBA PPARα-activation with Wy 14643 elicits a ''blind'' transactivation of the UCP-1 promoter which can prevent PPARγ-mediated UCP-1 mRNA transcription either by competition for the PPRE or by an unidentified post-transcriptional event.