Basal and stimulated activity of the c-fos promoter is reduced by triiodothyronine (T3) and retinoic acid (RA) in GH1 cells. We examined the influence of these ligands on the activity of reporter constructs containing the AP-1 site, the serum response element (SRE) and the cyclic AMP responsive element (CRE) of the c-fos promoter under control of an heterologous promoter. T3 and RA decreased the response of AP-1 and SRE sequences to phorbol esters, forskolin or serum but they did not reduce basal or forskolin-stimulated activity mediated by the CRE. Therefore, repression of c-fos gene expression by T3 and RA receptors appears to be exerted through transcriptional interference with the SRE and the AP-1 binding site of the promoter.