[3H]Tryptamine binding in rat brain is widely distributed with highest densities in the cortex, striatum and hippocampus. This binding is stereospecific and is potently displaced by tryptamine analogues and beta-carbolines. Phenethylamines also possess a weaker activity in displacing [3H]tryptamine. The strict structural requirements for binding to this site substantiate its unique character and suggest that it may represent a tryptamine receptor in the CNS.