THE effects of C-type natriuretic peptide (CNP) on the hypothalamo-pituitary-adrenal system response to different stressors was studied. Various doses of CNP (0.2, 2, 4 μg) were injected into the lateral cerebral ventricle of freely moving rats 30 min before stress and activation of the adrenal was measured by plasma corticosterone. CNP did not affect basal corticosterone secretion in the doses applied, but inhibited in a dose-dependent manner the increase in plasma corticosterone induced by ether stress, electric shock and restraint. CNP exerted a more profound inhibitory effect on the response to ether stress than on that to electric shock or restraint. These results suggest that CNP acts centrally and to a different extent on the responses to different stresses.