The hallucinogenic indoleamine drugs N,N-dimethyltryptamine (N,N-DMT), psilocybin, bufotenin, 5-methoxy-N,N-dimethyltryptamine, and N-methyltryptamine, increased rat plasma prolactin (PRL) levels. The increase in plasma PRL produced by N,N-DMT, psilocybin, and bufotenin was inhibited by methysergide, a serotonin receptor blocker. Parachlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, significantly potentiated the increase in PRL produced by N,N-DMT, and psilocybin. Parachloroamphetamine, a relatively selective toxin for serotonin neurons, also stimulated the increase in PRL produced by N,N-DMT. These results suggest that the indole hallucinogens stimulate PRL secretion by a serotonergic agonist mechanism. Bufotenin has been reported to pass the blood-brain barrier poorly, but of the indoles studied it had the most potent effect on PRL secretion. This raises the possibility that the serotonin receptors which promote PRL secretion may be outside the blood-brain barrier or that the central 5-HT receptors which mediate PRL secretion may be especially responsive to bufotenin.