The effect of lithium on serotonin (5-HT)-mediated responses in the brain was assessed by measuring changes in the prolactin (PRL) and growth hormone (GH) responses to L-tryptophan (LTP) in eight normal subjects. On the 4th day of lithium treatment the PRL responses were significantly enhanced, and this enhancement was still apparent after 20 days' treatment. In contrast, GH responses to LTP were not altered. Lithium had no effect on platelet 5-HT content, platelet imipramine binding and platelet 5-HT receptor binding. The ability of lithium to enhance some aspects of brain 5-HT function may be important in its mode of action in manic-depressive illness and may be particularly relevant to its potentiation of the antidepressant effect of tricyclic antidepressants.