The effects of cholinergic and adrenergic blocking agents on the period and amplitude of sustained oscillations in plasma levels of insulin and glucose were studied in 16 overnight-fasted conscious rhesus monkeys. Blood samples were withdrawn at 2-min intervals before and during or following administration of drugs that affect neurotransmission. Cholinergic blockade with atropine had no effect on the oscillations. alpha-Adrenergic blockade with phentolamine caused a rise in plasma insulin that lasted less than 10 min and was followed by a slight, although not consistent, decrease in mean insulin and a consistent small decrease in glucose. There was a sustained increase in heart rate, but no effect on the oscillations of insulin or glucose. beta-Adrenergic blockade induced by propranolol led to persistent decreases in mean plasma insulin 60% below the base line, small but variable decreases in glucose, and a sustained decrease in heart rate, but no change in period or relative amplitude of the oscillations in plasma levels of either insulin or glucose. General anesthesia with pentobarbital did not eliminate these oscillations. Our observations on the failure of the blockade of certain putative efferent pathways or depression of higher cortical centers to alter the period of the oscillations of insulin reduce the likelihood that the oscillations are transmitted from a pacemaker in the central nervous system.