Prostaglandin F2 alpha (PG-F2 alpha) was metabolized to different products by freshly isolated alveolar type II cells from adult male or pregnant rabbits. The type II cells from the adult male rabbits metabolized PG-F2 alpha to products which co-chromatographed on HPLC with 15-keto PG-F2 alpha and 13,14-dihydro-15-keto PG-F2 alpha, metabolites of cytosolic metabolism. The cells from the pregnant rabbit metabolized the prostaglandin to several polar metabolites. The major peak co-eluted with 20-hydroxy-PG-F2 alpha, a product dependent on cytochrome P-450 metabolism. The other polar metabolites were likely secondary oxidation products, formed by both the cytosolic 15-dehydrogenase and/or the 13,14-reductase and the microsomal omega-hydroxylase. No metabolism of PG-F2 alpha was observed in fractions of alveolar macrophages or tracheal cells of either adult male or pregnant rabbits. Fractions enriched in Clara cells (40-60% purity) showed little and variable metabolism of PG-F2 alpha, qualitatively similar to that observed with type II cells. However, data was inconclusive due to the low Clara cell purity and low activity.