To determine whether centrally mediated adrenergic tone modulates lipolysis, ketogenesis, or insulinopenia during starvation, four lean male subjects with complete cervical cord transection and six lean healthy male volunteers were fasted for 48 hr. Plasma glucose and insulin levels decreased to comparable levels in both groups. Plasma free fatty acid (FFA) and beta-hydroxybutyrate concentrations rose to peak levels 1.23 +/- 0.08 mmoles/liter and 4.2 +/- 1.0 mmoles/liter at 36 and 48 hr in normals, respectively. Cord-sectioned subjects had similar peak FFA (1.2 "/- 0.12) and beta-hydroxybutyrate (5.6 +/- 0.3) concentrations. Urinary catecholamine excretion in four normal subjects failed to increase during the fast. Since normal glucose, free fatty acid, beta-hydroxybutyrate, and insulin relationships were maintained in sympathectomized subjects, it appears that central adrenergic mechanisms are not essential for initiation of lipolysis, ketonemia, or the hypoinsulinemia of early starvation. These results provide additional evidence that these metabolic events are primarily related to insulinopenia.