The pulmonary uptake and accumulation of the three polyamines putrescine, spermidine and spermine by isolated ventilated and perfused rat lungs was investigated using 0.1, 1 or 5 mM concentrations of these compounds. The lung uptake of putrescine for all concentrations was greater than that of spermidine and spermine, but all three showed concentration-dependent linear uptake. A significant uptake of all three polyamines was also observed when incubated separately with rat lung slices for 60 min. Harmaline (0.4 mM), ouabain (0.2 mM) and perfusate with decreased Na+ (50 mEq/l) did not affect the uptake of any of the three polyamines by isolated perfused rat lungs or rat lung slice incubations. HPLC analysis of the whole lung or slices and media after perfusion or incubation studies, respectively, with polyamines did not reveal the presence of any metabolites. Likewise, the analysis of the lung homogenate incubated at 37 degrees C for 60 min with polyamines did not show any metabolites, confirming the absence of detectable pulmonary metabolism. These findings indicate a significant accumulation of polyamines in the rat lungs, accumulation predominantly occurring via simple diffusion, at variance with the reported active polyamine uptake process in the lung.