The objective of this study was to determine whether the posterior pituitary mediates the prolactin (PRL) releasing activities of serotonin and ether. Ovariectomized (OVEX) rats were subjected to posterior pituitary lobectomy (LOBEX) or sham surgery (SHAM). Either 1 or 12 days after surgery, rats were injected i.v. with 20 mg/kg b. wt. of 5-hydroxytryptophan (5-HTP), which is a precursor of serotonin. A second group of rats was exposed to ether vapors for 10 min. Blood was collected from a jugular cannula before and after the treatments and analyzed for PRL. On either 1 or 12 days after surgery, injection of 5-HTP increased plasma PRL levels 5-10 fold in both LOBEX and SHAM rats. This was followed by a decline to preinjection levels within 60-90 min. LOBEX and SHAM male rats which were injected i.p. with 50 mg/kg b. wt. of 5-HTP, also showed marked and similar elevations of plasma PRL levels 12 days after surgery. Exposure of OVEX rats to ether elicited a 2-3 fold rise in plasma PRL levels only on day 1, but not on day 12, after LOBEX. The ether-induced rise in PRL was similar in SHAM rats tested on both days. These results indicate that the 5-HTP-induced rise in plasma PRL levels is independent of the posterior pituitary, regardless of the sex, the route of drug administration or the length of time after surgery. In contrast, the PRL response to ether stress is diminished within 12 days after LOBEX. The evidence that the PRL responses to 5-HTP and to ether might be mediated via different neuronal mechanisms is discussed.