Markedly elevated levels of plasma atrial natriuretic peptide (ANP), which exhibit potent diuretic and vasoactive properties, has been well documented in patients with acute lung injury. We examined the physiological effects of additional smoke inhalation on plasma ANP concentrations in an ovine burn model. Seventeen sheep were instrumented to receive fluid and have physiological measurements taken. The burn group (n=8) received 40% body surface area third degree burn and the burn+smoke group (n=9) received the same burn plus 48 breaths of cotton smoke insufflation. The animals were resuscitated according to the Parkland formula with Ringer's lactate in the following 72 h period. Hemodynamic, oxygenation, fluid balance, and plasma ANP levels were serially determined. The effects of smoke inhalation manifested as deteriorated oxygenation, and increased fluid accumulation after a sustained initial shock period of more than 12 h. Plasma ANP levels in the burn+smoke group showed a biphasic elevation, whereas the burn group showed no appreciable changes throughout the whole experimental period. The initial increase in plasma ANP concentrations occurred immediately after injury (from 96+/-10 at baseline to 136+/-17 pg/mL at 3h after injury); thereafter, it decreased towards baseline value, followed by a second increase in the post resuscitation period (183+/-43 pg/mL at 72 h after injury). Decreased urine output and accentuated pulmonary vascular resistance in the combined injury group was observed between the two ANP level peaks, indicating that ANP release modified physiological responses to the burn+smoke injury.