This study was undertaken to search for an alternative experimental model in the evaluation of fentanyl-induced muscle rigidity. Unanesthetized, spontaneously ventilating Sprague-Dawley rats, and rats anesthetized with either ketamine or thiopental whose ventilation was mechanically controlled, were studied. Intravenous administration of fentanyl (25, 50, or 100 micrograms/kg) caused an increase in electromyographic (EMG) activity in both unanesthetized and ketamine-anesthetized, but not in thiopental-anesthetized, animals. Muscle rigidity was more prominently manifested in the gastrocnemius muscle, when compared with the rectus abdominis muscle. Hypoxemia was exhibited during the course of rigidity by both spontaneously ventilating and ketamine-anesthetized rats, but not by thiopental-anesthetized animals. In addition, unanesthetized, spontaneously ventilating rats developed hypercarbia and respiratory acidosis. The authors suggest that, in addition to using unanesthetized animals, EMG activity in the gastrocnemius muscle of rats anesthetized with ketamine in whom ventilation is controlled may provide an alternative approach in the evaluation of fentanyl-induced muscle rigidity.