AbstractThere is evidence for involvement of vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in control of prolactin secretion. In fact VIP‐ and PHI‐like immunoreactivities have been demonstrated in the hypotha/amic paraventricular nucleus and at the median eminence level. Using immunohistochemistry we have compared the distribution of immunoreactive VIP and PHI in the hypothalamus of male Sprague‐Dawley rats and BS rats, a rat strain which has a deficient release of prolactin after stressful stimuli. Quantitative information was obtained by radioimmunoassay for VIP. VIP‐ and PHI‐positive cell bodies were found in the parvocellular part of the paraventricular nucleus in colchicine‐treated rats and in nerve fibres within the median eminence of untreated rats to the same extent in both strains. Furthermore, intravenous injection of VIP caused a significant increase in serum prolactin tevets in both strains. However, at the median eminence level in BS rats, the blood vessels located in the lateral aspects of the median eminence did not show the dense VIP/PHI innervation seen in Sprague‐Dawley rats. Also, a thick VIP/PHI‐positive nerve bundle present on the surface of the median eminence of Sprague‐Dawley rats could not be seen in BS rats. Radioimmunoassay analysis revealed that VIP levels in the median eminence were twice as high in Sprague‐Dawley as compared to BS rats. Taken together, these results suggest that the defect in the prolactin release mechanism present in BS rats is not confined to the paraventricular system or the pituitary, but could be due to a deficit in VIP/PHI in fibres associated with portal vessels at the median eminence level.