Continuous negative-pressure therapy was used to assist ventilation in 19 spontaneously breathing patients, 6 months to 17 years of age, who developed progressive respiratory insufficiency (arterial PO2 less than 70 mm Hg despite a fraction of inspired O2 larger than or equal to 50 per cent) due to Pneumocystis carinii pneumonitis. Within 1 hour of therapy, arterial PO2 increased from a mean +/- SE of 61.9 +/- 3.7 to 75.4 +/- 7.0 mm Hg (P less than 0.05) and, by 6 hours, to 79.9 +/- 4.7 mm Hg (P less than 0.005). In the 14 survivors, these improvements were sustained and, within 24 hours, permitted a decrease in inspired O2 concentration from a mean +/- SE of 50.4 +/- 1.2 per cent to 40.1 +/- 1.6 per cent (P less than 0.005). By contrast, in nonsurvivors, O2 requirements could not be decreased significantly despite increases in negative pressure. Improvements in arterial oxygenation were associated with decreases in alveolar-arterial PO2 differences in all patients; however, significant decreases occurred only with pressures of -8 to -12 cm H2O. Higher negative pressures were ineffective and usually produced pulmonary air leak. Since the introduction of continuous negative-pressure therapy as a means of assisting ventilation in management of progressive respiratory insufficiency, the over-all survival rate among patients with Pneumocystis carinii pneumonitis at this institution has increased from 69 to 89 per cent.