Fibrinogen gamma-chains are derived from differential mRNA splicing resulting in polypeptide that differ in their carboxyterminal sequences as well as tissue distribution. We examined the expression of the rat fibrinogen gamma-chain mRNAs to determine the nature of the differential tissue expression of the gamma-fibrinogens. Here we demonstrate that the expression of the rat gamma B mRNA is tissue-specific. Northern blot analysis indicated that gamma A mRNA was expressed in liver, lung, brain and marrow, while the alternatively spliced gamma B mRNA was expressed only in liver. Three distinct full-length species of gamma B mRNA were identified in liver, indicative of multiple sites for polyadenylation that is suggestive of regulation at the level of 3' RNA processing. The restricted expression of gamma B mRNA in liver was contrasted by the ubiquitous expression of the gamma-chain promoter in brain and lung tissues that are not known for production of plasma coagulation proteins. The results of in situ hybridization showed that only gamma A mRNA was found in lung, localized to bronchiolar epithelial cells and chondrocytes but not smooth muscle or endothelial cells. Tissue-specific regulation of the gamma-chain gene results in compartmentalization of gamma B-fibrinogen to the circulation.