In three independent lines of transgenic mice, a 3.6 kb 5'-flanking sequence of the uroplakin II gene consistently drives the ectopic expression of a bacterial lacZ reporter gene in brain, in addition to its specific expression in the suprabasal layers of the urothelium. The ectopic expression in brain is especially noteworthy insofar as it is confined to structures comprising the limbic system. These findings provide additional evidence that the cells forming such functional systems share specific biochemical properties, and also indicate that this promoter may be useful as a tool for studying the effects of overexpression of proteins in anatomically and functionally defined central nervous system pathways.