In this study, we evaluated the effect of sodium nitroprusside (SNP), a vascular smooth-muscle relaxant, on lower esophageal sphincter (LES) pressure in the opossum. Resting LES pressure was monitored with a perfused sleeve sensor which allows accurate recording of LES pressure irrespective of axial LES motion. Intravenous pulse doses and infusion doses of SNP both caused significant decreases in both blood pressure and LES pressure. Les tone, however, was more sensitive to SNP than blood pressure. For example, an SNP pulse dose of 20 microgram/kg which lowered blood pressure only about 30% virtually abolished LES tone. A similar result was obtained for an SNP infusion dose of 10 microgram/kg/min. Tachyphylaxis to SNP did not occur for repeated pulse doses to 10 microgram/kg, but did develop during a 20-min infusion of 10 microgram/kg/min. The effect of SNP on LES pressure was not antagonized by propranolol, metiamide, haloperidol, atropine, phentolamine, or tetrodotoxin. We conclude that the potent depressant effect of SNP on LES tone is due to a direct action of the drug on sphincter smooth muscle.