We have shown that injecting corticotropin releasing factor (CRF) into inflamed rat paws causes the local release of endogenous opioids to inhibit pain. The purpose of the current study was to visualize CRF receptors by means of in vitro receptor autoradiography. We used I-125-CRF as a ligand on sections of popliteal lymph nodes, subcutaneous tissue of hind paws and spleen of rats. The density of I-125-CRF labelled receptors was higher in inflamed lymph nodes than in noninflamed lymph nodes (P=0.0431, Wilcoxon test). Similarly, the density of CRF receptors was significantly higher in inflamed than in noninflamed paws (P=0.0431, Wilcoxon test). This increase in CRF receptors indicates an upregulation of CRF binding sites in inflamed tissue. These findings are consistent with our in vivo studies which have shown potent antinoceciptive effects of locally applied CRF in inflamed but not in noninflamed tissue.