The present work was to study if the alpha-melanocyte-stimulating hormone (alpha-MSH) was involved in activation of the pituitary-adrenal axis (PAA) in rats. The hormone increased plasma corticosterone (CORT) level, and induced an anxiogenic response as indicated by results from the elevated plus-maze test. Intracerebroventricular administration of corticotropin-releasing factor (CRF) antiserum (1:10, 1:20 and 1:100 dilutions in 1microl volume), overcame both the anxiogenic response and the PAA activating effect induced by alpha-MSH (50 microg s.c.) in a concentration-dependent manner. CRF antibody at the doses applied did not modify either the elevated plus-maze responses or CORT level by itself. Our results reveal that both the anxiogenic and the PAA activating effects of alpha-MSH are mediated by CRF.