Instrumental responding for intravenous cocaine in rats at 85% of free-feeding weight was significantly decreased 50% by D-fenfluramine plus phentermine (D-Fen/Phen, 5 mg/kg of each for 1 day). A similar effect was obtained in normal-weight rats self-administering a cocaine - heroin mixture. Treating normal-weight animals with fluoxetine (5 mg/kg) for 4 days also significantly decreased cocaine self-administration by half, and then adding phentermine caused an additional decrease in cocaine intake. Animals that were well trained to self-administer drug did not self-administer intravenous D-Fen/Phen or Flu/Phen. The present results confirm that serotonergic drugs can decrease cocaine, or cocaine/heroin, self-administration in rats, and that phentermine adds to the effect. Based on related research with the same dose of D-Fen/Phen, it is suggested that effectiveness in reducing cocaine reinforcement is due in part to a satiating effect in which dopamine and acetylcholine are released in the nucleus accumbens.