To assess the role of serotonin release in the prolactin response to fenfluramine, rats were treated with fenfluramine alone or in combination with a dose of fluoxetine known to block fenfluramine-induced serotonin release. Fluoxetine pretreatment did not prevent fenfluramine-induced increases in prolactin. These findings indicate that fenfluramine-induced increases in prolactin are independent of serotonin release, and possibly involve direct post-synaptic actions of fenfluramine or one of its metabolites (norfenfluramine).