We have previously identified in fasting monkeys large amplitude, rapid oscillations in plasma levels of insulin, glucagon, and glucose. To determine whether such spontaneous oscillations also occur in man, we studied 9 healthy normal weight subjects and 11 obese volunteers (145-316% ideal body weight). During the morning hours after a 16-h fast, peripheral venous blood was withdrawn at precise 1- or 2-min intervals over 40-120 min. Spectral analysis of the assay results showed significant oscillations in plasma levels of insulin and glucose, with periods ranging from 8-16 min (P less than 0.05). In this range, the means of the oscillatory periods in normal weight subjects were 12.1 +/- 1.0 min for insulin and 11.2 +/- 0.8 min for glucose. The oscillatory periods on obese subjects were not different from those in normal weight subjects (12.4 +/- 0.7 min for insulin and 12.1 +/- 0.9 min for glucose). Periodicity in plasma levels of glucagon was observed in the range of 12-23 min. Based on cross-correlation analysis, the periodic fluctuations in insulin, glucose, and glucagon showed no consistent relationships; the patterns observed did not support the presence of feedback loops among these parameters as the mechanism of these spontaneous fluctuations. Our data indicate that basal plasma levels of insulin, glucagon, and glucose fluctuate rapidly in man. The physiological function of these oscillations is yet to be identified; they may play a role in the regulation of responsiveness of the respective target tissues or of their own release into the circulation.