Growth hormone (GH) is diabetogenic but has also been suggested to stimulate insulin release. Our aim was to study whether acute effects of GH on serum insulin and glucose concentrations can be observed when GH release is physiologically induced by GH-releasing hormone (GHRH), which is known to stimulate insulin secretion. We also studied the acute effects of GHRH as such on insulin release in vivo and in vitro. Female Sprague-Dawley rats were hypophysectomized (hypox) at 40 days of age. At day 188, rats received 1 microgram GHRH(1-29)/100 g body weight i.v. In sham-operated rats, GHRH induced a rise in serum GH from 36.5 +/- 1.9 ng/ml (time 0 min) to 560.0 +/- 13.3 ng/ml (5 min;) (n = 6; p < 0.001). In hypox rats, no measurable serum levels of GH were detected either before or after GHRH treatment. Serum insulin was unaffected by GHRH in both groups of animals. Serum glucose was higher in sham operated than in hypox rats (7.3 +/- 0.4 vs. 6.3 +/- 0.1 mM at 0 min; p < 0.01). Serum glucose did not rise following GHRH injection. In isolated rat islets, cultured for 3 days at 11.1 mM glucose, 0.1-10 nM GHRH stimulated basal insulin release at 3 mM glucose. To summarize, GHRH at high concentrations stimulates insulin release in vitro, but neither GHRH, at a concentration where GH secretion is greatly stimulated, nor GHRH-induced GH release, have any acute effects on serum insulin or glucose levels.