A method is described for the measurement of 15-keto-13,14-dihydrometabolites of PGE2 and PGF2alpha in peripheral human plasma. This involves purification by high performance liquid chromatography followed by determination of levels by combined gas chromatography-mass spectrometry using tetradeuterated analogs of the metabolites as internal standards. The levels of these metabolites in plasma are considered to be a more reasonable index of the entry of PGE2 and PGF2alpha into peripheral blood than are the levels of the corresponding primary prostaglandins. The endogenous levels of 15-keto-13, 14-dihydro-PGE2 and 15-keto-13,14-dihydro-PGF2alpha found in peripheral plasma are 33 +/- 10 pg/ml (SD; n=6) and 40 +/- 16 pg/ml (SD; n=6), respectively.