A competitive polymerase chain reaction (PCR) assay was developed to quantitate vitronectin (Vn) mRNA in murine tissues using a synthetic RNA as an external standard. Although the liver contained the highest concentration of Vn mRNA, significant levels were also detected in the brain (25-fold less) and in adipose tissue, heart, and skeletal muscle (100-fold less than liver). Lower concentrations also were detected in the lung, uterus, testis, and thymus, and little or no Vn mRNA could be detected in kidney, spleen, and blood. These results indicate that significant amounts of Vn mRNA are produced in extrahepatic organs. The regulation of Vn gene expression in vivo was studied in a murine model system in which acute systemic inflammation was induced by endotoxin administration. Plasma Vn levels increased 2- to 3-fold within 16 h after endotoxin administration and remained elevated for up to 72 h. This increase appeared to result from increased synthesis in the liver since the steady-state level of hepatic Vn mRNA increased 4-fold after endotoxin administration. Moreover, Vn mRNA levels in heart, lung, and brain were not significantly increased by endotoxin. These results suggest that Vn gene expression in vivo is regulated in a tissue-specific manner and identify Vn as a novel acute phase reactant.