Chimeric genes containing portions of the mouse myelin proteolipid protein (PLP) gene fused to the lacZ reporter gene were used to detect the effect of PLP intron 1 sequences on cell type-specific expression. A transfected fusion gene containing PLP intron 1 sequences was expressed in an oligodendrocyte cell line but not in a liver cell line, consistent with endogenous PLP gene expression. However, an analogous fusion gene missing the first intron was expressed in either oligodendrocyte or liver transfected cells. These studies suggest that transcriptional repressor element(s) located in PLP intron 1 are important in extinguishing expression in non-glial cell types and that the promoter alone functions in an indiscriminate manner. This moderately large intron (>8 kb) was sequenced to aid in future fine mapping of these cell-specific regulatory element(s).