Prostaglandin (PG) synthesis by human embryo lung fibroblasts in culture was determined with increasing population doubling. These cultures synthesized PGE2, PGF2 alpha, PGI2 (prostacyclin) and TXA2 (thromboxane A2) in response to fetal bovine serum or ascorbic acid. Changes in prostaglandin synthesis by these cells during aging were observed in response to serum or ascorbic acid. These included a shift from the synthesis of PGI2 and PGE2 to TXA2 and PGF2 alpha and finally to PGF2 alpha alone. We also observed a marked increase during aging in the release of precursor fatty acid from lipid stores upon stimulation with ascorbic acid. A parallel decrease in the ability to convert the released fatty acid to prostaglandins was detected.