Pancuronium bromide (Pavulon) is used to induce skeletal muscle paralysis in preterm infants, presumably for effective ventilatory support during acute respiratory failure. Twelve infants with respiratory failure were evaluated for sequential changes in pulmonary mechanics during continuous pancuronium administration (0.1 mg/kg every two to three hours) for more than 48 hours. The study weight of the neonates ranged from 980 to 2,950 g, and the postconceptional age ranged from 27 to 41 weeks. Pulmonary compliance, resistance, and resistive work of breathing were determined, using least mean square analysis technique, daily for three days and after discontinuation of pancuronium (even though there was no clinical improvement in ventilatory management). The dynamic pulmonary compliance decreased from 0.38 +/- 0.05 to 0.30 +/- 0.04 mL/cm H2O/kg (mean +/- SE) (P less than .05) and the total pulmonary resistance increased 51% from 115.6 +/- 21.3 to 174.9 +/- 27.3 cm H2O/L/s (P less than .005) during prolonged skeletal muscle paralysis. Upon discontinuation of pancuronium, the dynamic pulmonary compliance increased 43% to 0.43 +/- 0.4 mL/cm H2O/kg (P less than .05) and the total pulmonary resistance decreased by 41% (P less than .005). These data question the advisability of prolonged skeletal muscle paralysis in neonates and suggest the need for further detailed evaluation of the effects of prolonged paralysis on neonatal pulmonary mechanics.