The secretory phospholipase A₂ (sPLA₂) family in mammals contains more than 10 enzymes. In this study, we examined by immunohistochemistry the localization of six sPLA₂s (IIA, IID, IIE, IIF, V and X) in human heart, kidney, liver and stomach. In normal hearts, sPLA₂-IIA was detected in coronary vascular smooth muscle cells (VSMC) and sPLA₂-V in cardiomyocytes beneath the endocardium. In infarcted hearts, expression of these two enzymes was markedly increased in damaged cardiomyocytes, and expression of sPLA₂-IID and-IIE, which was undetectable in normal hearts, was elevated in damaged cardiomyocytes and VSMC, respectively. In infarcted kidneys, sPLA₂-IIA and-V were markedly induced in the uriniferous tubular epithelium. In livers affected by viral hepatitis, sPLA₂-IIA and-V were expressed in hepatocytes with fatty degeneration. In the gastric glands exhibiting intestinal metaplasia, sPLA₂-IIA was localized in the glandular base, sPLA₂-IID and-V in the glandular body epithelium, sPLA₂-IIE and-IIF in goblet cells in the foveolar epithelium, and sPLA₂-X in both glandular body epithelial cells and foveolar epithelial goblet cells. In the gastric submucosal tissues, sPLA₂-IIA and-IIE were located in VSMC and sPLA₂-V was in the interstitial fibroblasts. In addition, sPLA₂-IIA,-IIE,-IIF and-X were highly expressed in gastric signet ring cell carcinoma. Thus, individual sPLA₂s exhibit unique cellular localizations in each tissue, suggesting their distinct roles in pathophysiology.