In vivo oscillations of pancreatic peptides are recognized in primates. To determine whether such oscillations also occur in other mammalian species and to examine their underlying mechanisms, portal vein levels of insulin, C-peptide, glucagon, somatostatin, pancreatic polypeptide (PP), and glucose were measured simultaneously at 1- or 2-min intervals in nine conscious dogs. For comparison with primates, additional experiments were conducted in baboons and humans. Computer-assisted pulse identification for both raw and smoothed data was performed and spectral estimations calculated after detrending. Concomitance and comovement between the fluctuations of the various peptides and glucose were tested. Prominent pulses at 10- to 14-min intervals were detected most regularly for insulin and glucagon and were frequently reflected in PP and somatostatin levels. Corresponding relative increments in plasma concentration averaged 54% for insulin, 16% for glucagon, 25% for PP, and 24% for somatostatin. Insulin pulses were concomitant with glucagon pulses in 80% of the cases. Pulses of PP were less frequent, although consistently associated with insulin pulses. Somatostatin pulses were less consistently associated with those of other peptides. Peptide oscillations were unrelated to glucose changes. Spectral analysis confirmed these results with peaks in the 10- to 14-min range for all peptides but no significant periodicity for glucose. No consistent delays or advances between the oscillations of the various peptides could be demonstrated. It is speculated that oscillatory behavior in the pancreas may be related to a central pacemaker mechanism, which involves insulin tightly coupled to glucagon, entraining the fluctuations of PP, and, inconsistently, of somatostatin.