The receptor pharmacology of the human sweat gland was studied in vivo. The axon-reflex response was mediated by nicotinic receptors which were activated by nicotine and acetylcholine, but not pilocarpine, and inhibited by hexamethonium. The direct response was mainly muscarinic, responding to pilocarpine and acetylcholine. A component of the direct response was nicotinic, since it was activated by nicotine and blocked by hexamethonium in a dose-dependent manner. The axon-reflex response to nicotine and acetylcholine was partially blocked by pilocarpine, especially when application of pilocarpine preceded the procedure. The inhibition of the nicotinic response may be secondary to M1 antagonism since pilocarpine is an M2 agonist and M1 antagonist and pirenzepine, a specific M1 antagonist, caused similar effects as pilocarpine.