Exposure of neonatal Balb.B mice to a variant of Gross murine leukemia virus, termed WB91-GV, resulted in selective white matter infection within the central nervous system. Viral antigens were detected in brain sections of animals inoculated by either intracerebral or intraperitoneal routes, but were only seen in mice exposed within the first day after birth. This distinct tropism was confirmed by virus replication and gp70 expression in isolated glial cultures in vitro. Analysis of gp70 expression in highly enriched glial subpopulations indicated that oligodendrocytes and perhaps a subset of astrocytes were the targets of this infection.