Abnormal fat metabolism plays an important role in the pathogenesis of obesity-related type 2 diabetes mellitus. This study examined whether free fatty acid levels (FFAs), like insulin levels, oscillate rapidly in plasma. Peripheral and portal blood samples from dogs were assayed for FFA, glycerol, glucose, and insulin. FFA and glycerol showed correlated oscillatory profiles, with about 8 pulses/hour. Omental lipolysis was also pulsatile, with about 10 pulses/hour, and insulin levels oscillated rapidly in plasma with about 7 pulses/hour. We applied an insulin clamp, beta-adrenergic blockade, or both together, to determine the driving force behind the FFA oscillation, and we analyzed our findings by approximate entropy (ApEn) for which lower values suggest regular pulses and higher values suggest disorder. Under basal conditions, ApEn was 0.3 +/- 0.2. With insulin not oscillating, FFA still cycled at about 9 pulses/hour and the ApEn was 0.2 +/- 0.1. In contrast, beta-blockade, either in the presence or absence of an insulin clamp, removed the FFA oscillation in three of nine dogs. In the other six dogs, the oscillatory profile was unchanged, but ApEn was significantly higher than basal values, suggesting that the regularity of the profile was disrupted. These results suggest that the FFA oscillation is driven by the central nervous system, not by insulin.