Myelination in the central nervous system requires synthesis by oligodendrocytes of enormous amounts of lipids and proteins for incorporation in the developing myelin membranes. To approach the regulatory events coordinating the transcriptional activation of the genes that encode myelin proteins, we examined control of the myelin basic protein (MBP) locus. MBP plays a major role in myelin compaction. During development, MBP is already expressed in mature non-myelinating oligodendrocytes. Here we show that, in transgenic animals in which the E. coli lacZ reporter gene is under the control of increasingly large portions (256, 1900 and 3200 bp) of the MBP promoter, 5' of the initiation of transcription site, reporter gene expression was initiated after myelin formation had started. This delayed expression of the transgene compared to MBP, strongly suggests that premyelinating expression is dependent on regulatory elements located outside of the 3200 bp sequence studied, while expression occurring at the time of myelin formation is dependent on the proximal promoter sequence.