Abstract Central α 2-adrenergic function is often inferred from the growth hormone (GH) response to clonidine, despite the drug's known hypnotic effect and the accepted cholinergic mechanism for sleep-related GH secretion. We examined the effect of daytime sleep on GH secretion in normal men taking placebo or clonidine orally, using a two-group blind design (placebo, clonidine; n=9 each). Each subject participated in two morning sessions monitored by polysomnography: wake (sleep actively prevented) and sleep (subjects asked to sleep for 3 hr after receiving placebo or clonidine). Blood samples were drawn at times -15 min, 0, and every 30 min for 3 hr after the test dose was given. The total sleep time was similar for both groups. The placebo/wake group had lower GH responses than the other three groups. None of the GH responses in the clonidine/sleep group were significantly different from those in the placebo/sleep group; and the peak GH μg/L, mean±SD) was 16.9±10.9 vs. 14.6±10.5, respectively. We conclude that the GH response to clonidine may not be indicative of α 2-adrenergic function if sleep is permitted during the test.