Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of prostaglandin (PG) D(2), has been found to be present in the atherosclerotic plaque of the human coronary artery and also to be detectable in human serum. This multicenter cooperative study was designed to establish the diagnostic value of measuring serum L-PGDS for coronary artery disease. The study included 1013 consecutive patients suspected of having stable coronary artery disease who underwent diagnostic coronary angiography. Peripheral blood was collected prior to angiography. The serum level of L-PGDS, as determined by a sandwich ELISA, was 58.1 +/- 2.2, 62.0 +/- 1.8 and 80.6 +/- 2.6 microg/dl for patients with no stenotic lesion (N, n=241), single-vessel coronary artery disease (S, n=351), and multi-vessel coronary artery disease (M, n=421), respectively (N vs. S; P<0.001, S vs. M; P<0.01, N vs. M; P<0.001). Multiple regression analysis indicated that the most powerful independent predictor of the coronary severity score (Gensini Score) was the L-PGDS level (R=0.55, P<0.0001). The serum L-PGDS level is suitable to evaluate the severity of coronary artery disease. The measurement of serum L-PGDS can be a strategy for screening of stable coronary artery disease prior to coronary angiography.