We have examined the effects of hGRF on cyclic AMP and glycogen levels in mouse cerebral cortical slices. hGRF-44-NH2 and hGRF-28-OH did not stimulate cyclic AMP formation nor glycogenolysis and did not antagonize the stimulatory effects of VIP on cyclic AMP formation and glycogenolysis. These observations indicate that despite the structural homologies with VIP, hGRF does not interact with VIP receptors coupled to adenylate cyclase in mouse cerebral cortex. This is in contrast with observations in other tissues and species, such as rat and human intestinal epithelial membranes and rat pancreas. We have also compared the effects of hGRF, VIP, PHI and secretin on Growth Hormone (GH) release and cyclic AMP levels in anterior pituitary cells in vitro. VIP and PHI, but not secretin, promote at a high concentration (10(-6) M) a small but significant release of GH. This GH release is accompanied by increases in cyclic AMP levels. The concentration of VIP and PHI required to elicit these effects is high and suggests that VIP and PHI act as low affinity pharmacological analogs of hGRF on hGRF pituitary receptors.