The metabolism of arachidonic acid (AA) has been determined in four lines. The cell lines NCI-H69 and NCI-H128 are derived from small cell carcinomas of the lung (SCCL), and the cell lines NCI-H322 and NCI-H358 are derived from pulmonary adenocarcinomas. AA did not undergo metabolism when incubated with suspensions of NCI-H69 and NCI-H128 cells. Significant metabolism did occur when AA was incubated with monolayers of unstimulated NCI-H322 and NCI-H358 cells. A single metabolite of AA isolated from these cells was identified as prostaglandin E2(PGE2) via combined gas chromatography-mass spectrometry (CG-MS). Additional details of arachidonatemetabolism in monolayers of these cells are contained in a separate report (see No. 07173-01). The preferential synthesis of prostaglandins by certain types of human lung carcinomas may have direct clinical implications. Elevated levels of production of selected prostanoids in patients could be indicative of the presence of certain cell types of lung carcinomas. The selective synthesis of prostanoids by certain human lung carcinomas may also confer significant capabilities for P-450 monooxygenase-independent metabolism of antitumor agents and other xenobiotics. The possibility that prostaglandin synthesis may be a unique feature of certain types of human lung carcinomas and the role of the prostaglandin endoperoxide synthase (PES) system in the metabolism of antitumor agents and other xenobiotics are under investigation.