Gastrin-like immunoreactive substances have been reported as occurring in both digestive tract tissues and nervous system, including the hypothalamus and the anterior and posterior pituitary. The carboxyterminal tetrapeptide shared by gastrin and cholecystokinin, which represents the bioactive site of both hormones, has been shown to be a secretagogue for insulin and glucagon and it might have a neurotrasmitter function. As small gastrin-like peptides may also play a role in the regulation of anterior pituitary hormones, the present study deals with the in vivo effect of pentagastrin on the release of growth hormone (GH) and prolactin (PRL). Six healthy volunteer males and six healthy volunteer females were studied. All females subjects were in the early follicular phase of the normal menstrual cycle and all subjects were not taking or had been taking any drug known to affect GH or PRL secretion. A continuous intravenous infusion of pentagastrin (1.5 micrograms/kg/h) was administered to all the subjects for a time of 3 hours. In males pentagastrin infusion resulted in a significant increase in GH concentration from basal values (P less than 0.01 at 60 min). In females pentagastrin infusion did not affect GH levels. PRL levels were not affected at all by intravenous pentagastrin infusion both in males and females. The exact understanding of pentagastrin action on GH release awaits further investigation. The different pattern between male and female subjects suggests a sexual hormone influence on the hypothalamic-pituitary sites of action of pentagastrin in vivo. Our data did not confirm a stimulatory effect of pentagastrin on PRL secretion in normal subjects.