Immature and nearly mature fetal rabbits (gestational age 27.5 and 29.5 days, respectively) were obtained by hysterotomy and tracheotomized at birth. Immature rabbits received, via the tracheal cannula, 2.5 ml/kg of either normal saline, porcine surfactant (60 mg/ml), 1 mM amiloride in normal saline, or a mixture of surfactant and amiloride; nearly mature rabbits received either normal saline, or 1 mM amiloride in saline. The neonates were ventilated with a tidal volume of approximately 10 ml/kg for 0-60 min (immature animals) or 0-120 min (nearly mature animals). The lungs were then excised for determination of wet lung weight/body weight ratio (LW/BW). The right lung was further processed for quantification of extravascular lung water (EVLW) per unit dry lung weight, and the left lung fixed for measuring the size of perivascular 'cuffs' (adventitial tissue including lymphatics) in histological sections, using vascular lumen as reference volume. Immature animals receiving surfactant had improved compliance and smaller perivascular cuffs in comparison with the other groups. In immature animals amiloride had no effect on compliance, LW/BW, and EVLW, but reduced perivascular cuff size at 15 min. Nearly mature animals receiving amiloride had higher values for LW/BW and EVLW at 120 min, and lower perivascular cuff size at 15, 60, and 120 min, in comparison with saline-treated litter-mates. We conclude that surfactant improves lung-thorax compliance and reduces perivascular fluid accumulation in immature newborn animals without influencing total lung water content, and that amiloride retards fetal lung liquid resorption in nearly mature newborn animals without affecting lung-thorax compliance during artificial ventilation.