The basal plasma insulin, glucagon, and glucose concentrations of 28 normal subjects were measured at 1-min intervals for periods of 45–120 min. Regular plasma insulin and/or glucagon cycles were detected in 11 subjects by autocorrelation (mean periods 13.1 and 13.7 min, respectively). Individual plasma insulin cycles were defined in all subjects (mean period 10.7 min, amplitude 1.1 mU/L), and were associated, after averaging, with plasma glucagon (amplitude 5.5 pg/ml) and plasma glucose (0.02 mmol/L) cycles. There was a significant correlation between the amplitudes of simultaneous plasma insulin and glucagon cycles (r = 0.23, P = < 0.05, N = 124). Cross-correlation demonstrated a delay of 2 min between the changes in plasma insulin and glucagon. No comparable oscillations in plasma pancreatic polypeptide were detected. The synchronous pulsatile secretion of glucagon and insulin may be a mechanism by which insulin's hepatic effects are limited, thereby maintaining hepatic glucose production but allowing sufficient peripheral insulin concentrations to inhibit excessive catabolism. The simultaneous pulses of insulin and glucagon may be stimulated by a pacemaker, with the A-B intercellular connections producing insulin and glucagon synchrony.