The direct effects of growth hormone (GH) on the endocrine pancreas were studied in isolated islets of rats. To study GH-induced insulin release, islets were incubated in RPMI 1640 medium containing 1 or 10 micrograms/ml of bovine GH for 120 minutes. Islets incubated in the absence of GH served as controls. During the incubation, GH significantly increased the insulin concentration in the medium. To study the effect of GH on subsequent glucose-induced insulin release, islets were preincubated with GH; then the islets were transferred to perifusion chambers and after a 30-minute stabilization period with 2.8 mM glucose, the islets were stimulated by addition of 16.7 mM glucose for 60 minutes. These perifusions were performed in the absence of GH. Glucose-induced insulin release from control and GH-pretreated islets peaked at five minutes during the first phase (0-8 minutes) and plateaued at 25 minutes during the second phase (9-60 minutes). Preincubation with GH (1 microgram/ml) did not change baseline or first phase release, but significantly suppressed the second phase of insulin release. When islets were preincubated with 10 micrograms/ml of GH, both phases of glucose-induced insulin release were suppressed; the total amount of insulin released by GH-pretreated islets was suppressed by 36.6% during the subsequent glucose stimulation period. These data indicate that GH stimulates insulin release by itself (GH-induced insulin release) but inhibits subsequent glucose-induced insulin release in a dose-dependent manner.