Postnatal exposure to high levels (4%) of lead (Pb) have been shown to disrupt myelin formation and result in abnormal conduction of nerve impulses, components necessary for information processing in the CNS. To investigate whether the pathological changes in myelin, due to Pb exposure, might be partially mediated by modulations of the expression of genes involved in CNS myelin, we have examined the developmental profiles of the proteolipid protein (PLP) and myelin basic protein (MBP), two major structural constituents of CNS myelin and 2',3'-cyclic nucleotide 3' phosphodiesterase (CNP), a non-structural enzyme associated with myelin formation. Rat pups were postnatally exposed, from birth to weaning, to moderate amounts of Pb (0.2%), in the drinking water of the dam, and their frontal cortices were assayed for changes in the expression profile of the above genes by Northern Analysis. On PND 20, Pb resulted in a dramatic stimulation of the mRNA levels of PLP and a small increase in MBP mRNA levels, but had no effect on the CNP message. These data suggest that moderate levels of Pb selectively interfere with the gene expression of structural proteins of CNS myelin and may thus influence the composition of myelin in this way.