The effect of papaverine on the albumin permeability-surface area product (PS), reflection coefficient (σ), and capillary filtration coefficient (K(f)) was examined in isolated rabbit lungs. Because PS and K(f) are functions of vascular surface area and permeability, we also compared papaverine with two other means of maximizing lung surface area: isoproterenol (1 x 10-7 M) and a mild increase in vascular pressure. Only lungs perfused with 0.1 mg/ml papaverine were significantly different from control. PS increased from control (2.80 ± 0.16 to 5.53 ± 0.20 ml · min-1 · g dry lung-1 x 10-2), whereas σ decreased from control (0.92 ± 0.01 to 0.78 ± 0.03). K(f) after papaverine was significantly lower than baseline predrug K(f) (5.60 ± 0.78 to 4.56 ± 0.53 ml · s-1 · cmH2O-1 · g dry lung-1 x 10-3). However, this group's predrug K(f) was higher than that of any other group. Our results indicate that papaverine increases albumin permeability and decreases endothelial selectivity. The isolated perfused lung appears fully recruited, because K(f) and PS did not increase with isoproterenol or increased vascular pressure. Papaverine should be used with caution in the Ringer-perfused lung.