In a double-blind multicenter study versus placebo, the therapeutic effects of ambroxol (10 mg/kg, i.v. twice daily for 7 days) were studied in an appropriately selected population with severe respiratory failure. Treatment was given to 28 neonates with birth weight less than or equal to 2,000 g, appropriate for gestational age with idiopathic respiratory distress of such severity as to require assisted ventilation (IMV or IPPV) within 12 h of birth. The preliminary results showed that ambroxol treatment, and not placebo, increased survival, reduced the time during which mechanical ventilation was required and improved the FiO2/PaO2 ratio and the biochemical indices of pulmonary maturity. This latter improvement suggests that the amelioration of the IRDS clinical picture and the reduction of ventilatory requirement might be due to an increase in pulmonary surfactant. No side effects attributable to ambroxol therapy were observed in the treated infants.