Effects of neuroleptic agents on rat skeletal muscle contracture in vitro. The purpose of this investigation was to examine and compare the effects of both in vivo pretreatment and in vitro treatment with the neuroleptic agents droperidol, haloperidol, and trifluoperazine on skeletal muscle contracture using an in vitro model. Strips of normal rat diaphragm were challenged with succinylcholine and halothane (halothane: 1% and 3%) subsequent to either in vitro administration (10-100 microM) or in vivo pretreatment (0.35-2.80 mg/kg) with droperidol, haloperidol, or trifluoperazine. After equilibration, maximum increases in tension were recorded and mean data analyzed by analysis of variance (P less than 0.05). When either droperidol or trifluoperazine was administered in vivo, contracture values after exposure to succinylcholine and halothane were significantly decreased. After in vivo pretreatment with haloperidol or in vitro administration of droperidol, succinylcholine-induced contractures were significantly reduced; contractures subsequently induced by halothane did not significantly differ from that of controls. In vitro treatment with haloperidol and trifluoperazine, however, produced significant increases in tension in muscles exposed to succinylcholine and halothane. This study provides evidence that droperidol may be considered a safe anesthetic adjunct in malignant hyperthermia-susceptible patients, and, additionally, that caution should be exercised when interpreting results from studies in which contracture testing is performed on muscle from patients treated with neuroleptic agents. 