Two of 30 patients with esophageal varices had respiratory distress develop within 8-24 h of esophageal sclerotherapy. Evidence of aspiration and sepsis were absent in these two patients with the clinical picture of adult respiratory distress syndrome. To investigate the possible etiologic role of sodium morrhuate in this syndrome, a sheep model was established and pulmonary hemodynamics, lung lymph flow, and albumin concentration were measured before and after the intravenous injection of 2.5-15.0 cm3 of sodium morrhuate. In all 8 animals studied, mean pulmonary artery pressures increased from 11.6 +/- 2.8 to 32.8 +/- 4.9 mmHg (p less than 0.01) 30 s after injection. These pressures returned to baseline values over 120 min. Lymph flow increased from 0.91 +/- 0.89 to 2.8 +/- 1.5 ml/30 min at 90 min postinjection (p less than 0.05) and returned to baseline values in animals monitored for 6-8 h. The lymph/plasma albumin ratio decreased from 0.856 +/- 0.08 to 0.74 +/- 0.01 (p less than 0.05) 120 min postinjection. Pulmonary edema was not evident histologically or gravimetrically (wet/dry weight ratio was 3.65 +/- 0.3 and not different from normal). It was concluded that sodium morrhuate injection in sheep causes marked but transient pulmonary hypertension associated with an increased lymph flow of relatively protein-poor lymph. Sodium morrhuate esophageal sclerotherapy may affect pulmonary hemodynamics and contribute to respiratory difficulties in patients.