We hare isolated, napped and aequenced adipain, the adipocyte differentiation-dependent serine protease gene. This gene, which is present in a single fora in the mouse, spans 1.7 kilobases and contains five exons. While the basic exon structure characteristic of serine protease genes is conserved in adipsin, there is also a fusion of two exons that are separate in other serine proteases. The sequence data also suggests a mechanism of alternative splicing which appears to account for the generation of two adipsin oRNA species differing by only three nucleotides and encoding two different signal peptides. To investigate the control of adipsin expression we have examined the effects of tumor necrosis factor (TNF) on adipocytes. The level of adipsin RNA is dramatically decreased by hormone treatment, but the change occurs Bore slowly than for other fat cell aRNAa, such as glycerophosphate dehydrogenase. These results show that adipsin is a novel serine protease gene whose expression is regulated by a macrophage-derived factor which modulatea expression of other adipocyte-specific RNAa.