The effect of adrenergic receptor-blocking agents upon plasma levels of human pancreatic polypeptide (hPP), human GH (hGH), immunoreactive insulin, and glucose during graded submaximal exercise was ascertained in six healthy nonobese males. Subjects exercised from 0--27 min on a motor-driven treadmill and received infusions from -10 to 40 min of either 1) saline, 2) saline plus phentolamine (0.5 mg/min; alpha-adrenergic blockade), or 3) propranolol (3 mg) from -10 to -5 min, followed by saline plus propranolol (0.08 mg/min; beta-adrenergic blockade). During saline-exercise, mean plasma hPP rose from a mean (+/-SE) basal level of 45 +/- 11 to 149 +/- 51 pg/ml at 27 min, whereas with phentolamine-exercise, the maximal level reached by mean plasma hPP (305 +/- 28 pg/ml) was significantly greater than that with saline (P less than 0.05). During propranolol-exercise, mean plasma hPP did not rise significantly above the basal level. The incremental area under the hPP curve for phentolamine-exercise also was significantly greater than that for saline-exercise or propranolol-exercise. The changes in plasma hGH during and after saline-exercise correlated with those of hPP, but the effects of phentolamine and propranolol upon exercise-induced increases in hGH were opposite to the effects upon hPP. The exercise-induced fall in immunoreactive insulin was accentuated with propranolol and abolished with phentolamine. It is concluded that 1) submaximal exercise stimulates secretion of hPP and hGH, 2) adrnergic mechanisms participate in exercise-induced increased secretion of hPP (beta-adrenergic stimulation augments secretion and alpha-adrenergic stimulation inhibits secretion), and 3) adrenergic effects which modulate exercise-induced secretion of hPP and insulin are in parallel but are opposite to those that modulate the secretion of hGH.