OBJECTIVE The release of growth hormone (GH) from the anterior pituitary is partly under cholinergic control. Pyridostigmine, the acetylcholinesterase inhibitor, releases GH by this mechanism. Pyridostigmine/GH responses have been reported as enhanced in depression. The aim of the current study was to examine such responses during a manic episode. METHODS A between subjects design was employed. METHODS Seven male manic patients and seven male healthy controls were studied. They were matched in terms of age and body mass index. METHODS GH response to pyridostigmine (120 mg) challenge was measured as the net increase above baseline. Cortisol levels were also measured. RESULTS Release of GH in the manic patients was significantly enhanced and their baseline cortisol levels were elevated. CONCLUSIONS These results demonstrate enhanced pyridostigmine/GH responsiveness in mania which may be due to enhanced somatostatin tone or increased cholinergic receptor responsivity.