Endothelial lipase (EL), a new member of the triacylglycerol lipase gene family, is a key enzyme in HDL metabolism. The EL expression pattern in humans was reported to be unique and complementary to that documented for lipoprotein lipase. The regulatory elements responsible for the tissue-specific EL expression are not identified yet. In order to confine these sequences to a defined region of the EL promoter, we analyzed EL mRNA expression in human EL transgenic mice expressing EL under the control of the endogenous human promoter. We identified small intestine, mammary gland, adipose tissue and the adrenal gland as previously unknown tissues to express EL. Our data demonstrate that regulatory elements within 11.4 kb of 5' and 9.9 kb of 3' human EL flanking region promote the expression of EL in small intestine, ovary, testis, mammary gland, brain, lung, aorta, adipose tissue and the adrenals, whereas regulatory sequences located between 27.4 and 11.4 kb of 5' or 9.9 and 48.7 kb of 3' human EL flanking region seem to be responsible for kidney-specific EL expression.