Changes in plasma concentrations of corticosterone and beta-endorphin (beta-END) were determined in male rats after treatment with the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or the non-selective 5-HT agonist 6-chloro-2-(1-piperazinyl)pyrazine (MK-212). The administration of either 8-OH-DPAT or MK-212 increased plasma concentrations of both corticosterone and beta-END in a dose-related manner. The corticosterone and beta-END responses to 8-OH-DPAT were antagonized by spiperone and (-)-pindolol, both of which have been shown to have high affinity for the 5-HT1A binding site. In contrast, antagonist which are selective for the 5-HT2 receptor or non-selective 5-HT antagonists were without effect on the hormone responses to 8-OH-DPAT. The MK-212-induced increase in plasma concentrations of corticosterone and beta-END were not affected by treatment with the 5-HT1A antagonists spiperone and (-)-pindolol. However, the corticosterone and beta-END responses to MK-212 were attenuated by the selective 5-HT2 antagonists ketanserin, ritanserin and altanserin, as well as by the non-selective 5-HT antagonist metergoline. It is concluded that stimulation of either 5-HT1A or 5-HT2 receptors results in an activation of the hypothalamic-pituitary-adrenal axis in the rat.