After delivery by cesarean section at 133-136 days gestational age, 18 lambs were supported with infant ventilators. Peak inspiratory pressure was the only ventilator setting that was changed in an attempt to normalize PCO2. The lambs were retrospectively divided into two groups based on their respiratory status before treatment. Ten lambs with PCO2 values of 38 +/- 2 mmHg (mean +/- S.E.) at 5 h of age were treated with a 15-ml suspension containing 50 mg natural sheep surfactant lipid/kg body weight. After surfactant instillation, pH fell, PCO2 increased and compliance/kg decreased transiently. Surfactant treatment did not reduce the respiratory support that these lambs required. Eight lambs with PCO2 values of 68 +/- 3 mmHg at 3 +/- 0.8 h of age responded to surfactant instillation with a decrease in PCO2 and an increase in PO2 and pH. In both groups of lambs heart rates, mean aortic pressures, and mean pulmonary artery pressures changed little after surfactant instillation. Cardiac outputs and regional blood flows measured before and after surfactant treatment were unchanged. Instillation of surfactant suspensions to premature lambs did not adversely affect cardiovascular status; however, some lambs did have a transient deterioration of lung function after surfactant instillation.