Uptake of paraquat (PQ; 10 microM) into lung cell fractions enriched in alveolar type II cells or Clara cells was linear with time, and after 60 min the intracellular concentration was approximately 10-fold higher than that in the medium. In contrast, alveolar macrophages were not able to accumulate PQ from the extracellular medium. PQ uptake in preparations of type II and Clara cells, but not alveolar macrophages, was inhibited by an equimolar concentration of putrescine or spermidine and by a combination of the metabolic inhibitors, potassium cyanide and iodoacetate (1 mM each). The reduction of PQ (1 mM) under anaerobic conditions was investigated in lung cells by ESR spectroscopy. The amplitude of the ESR signal of the PQ radical increased with time with intact or sonicated type II and Clara cell preparations, but with macrophages it increased only when the cells were sonicated. The signal in sonicated cells but not whole cells was decreased by addition of antibodies to NADPH-cytochrome P-450 reductase, suggesting that the PQ radical is generated intracellularly under these conditions.