The clinical efficacy, side effect liability, and hormonal effects of two prototypic pharmacologic agents were evaluated for the management of chronic myogenous facial pain in a double-blind, randomized, controlled clinical trial. Thirty-nine subjects (35 women, 4 men) with daily or near-daily orofacial pain of at least 3 months' duration and tenderness to palpation of masticatory muscles participated. Patients were randomly allocated to one of four treatments: placebo, diazepam, ibuprofen, or the combination of diazepam and ibuprofen, Pain, mood, muscle tenderness, maximal interincisal opening, and plasma levels of B-endorphin were measured following 2-week baseline and 4-week treatment periods. Pain, as measured by a visual analog scale, was significantly decreased in the diazepam and diazepam plus ibuprofen groups but not for the ibuprofen or placebo groups. Analysis of variance showed a significant drug effect for diazepam but not for ibuprofen, indicating that pain relief was attirbutable to diazepam. No significant changes were noted in muscle tenderness, interincisal opening, or plasma B-endorphin level. This study supports the efficacy of diazepam in the short-term management of chronic orofacial muscle pain. The lack of effect following administration of an anti-inflammatory analgesic suggests that inflammation is not the basis for chronic muscle pain in the orofacial region, and that the analgesic effect of such medications is not sufficient for pain relief in this condition.