Midazolam differs from diazepam in that midazolam is water-soluble, more potent and has a shorter elimination half-life (t1/2). To date, it has been used primarily for induction of anesthesia and as an anesthetic supplement. Diazepam has been shown to decrease the catecholamine response to perioperative stress. This study determined the extent to which midazolam influences the physiological and hormonal responses that are evoked by a nitroprusside-induced hypotensive challenge. Plasma levels of epinephrine, norepinephrine (NE), cortisol, and renin activity, as well as hemodynamic performance were measured in dogs anesthetized with enflurane-nitrous oxide-oxygen. Midazolam 0.2 mg/kg i.v. administered prior to a 30% decrease in mean blood pressure statistically attentuates the increase in plasma catecholamines. The cortisol and renin increases that occurred in response to the hypotension were not affected appreciably by midazolam. Hemodynamic changes due to midazolam were minimal, with only a transient 8-10% decrease in mean blood pressure observed. The findings of this study demonstrate that midazolam, like diazepam and fentanyl, can reduce the physiological and hormonal response to hypotensive episodes that occurred during the course of anesthesia and surgery.