Secretion of pituitary immunoreactive beta-endorphin is hypothesized to modulate the perception of pain. The present study examined this question by evaluating the effects of intravenous placebo or dexamethasone (0.1, 0.32, or 1.0 mg) on suppression of immunoreactive beta-endorphin secretion and development of postoperative pain after the surgical removal of impacted third molars in 48 patients. Compared with placebo, all doses of dexamethasone suppressed the postoperative increase in circulating levels of immunoreactive beta-endorphin. Patients administered 0.1 mg dexamethasone reported greater levels of pain, compared with those given placebo, from 60 through 120 minutes after surgery. Postoperative pain for the 0.32 and 1.0 mg doses did not differ from that for the placebo group. The increased pain after suppression of beta-endorphin release by the low dose of dexamethasone suggests that pituitary secretion of immunoreactive beta-endorphin alleviates postoperative pain under these conditions.