Myelin basic protein (MBP) is a major myelin constituent produced by oligodendrocytes in the central nervous system (CNS). Expression of MBP was considered to be a marker for oligodendrocyte differentiation and myelination in the developing CNS. In this study, expression of myelin basic protein (MBP) and its messenger RNA (mRNA) was examined in human embryos and fetuses ranging in age from 5 to 20 gestational weeks (g.w.). We were able to demonstrate that MBP antibody labels cells in both human nervous and non-nervous tissues beginning from early embryonic life (5-6 g.w.). MBP positive (MBP+) cells were rounded, with either no cell processes or only 1-2 short processes, and were located in caudal regions of the CNS. MBP+ cells were also observed in the non-nervous tissue, such as leptomeninges, choroid plexus, and connective tissues. A number of MBP+ cells in nervous and non-nervous tissues were morphologically similar to macrophages and showed a positive reaction to macrophage-microglia markers: lectin (RCA-1) and the monoclonal antibody (EBM-11) to human macrophage antigen CD68, whereas they were negative for neuronal, astroglial, or marker for oligodendrocyte progenitors. At the same embryonic age, 5 g.w. and onward, the MBP mRNA was observed in the CNS by in situ hybridization. The results of this study show that MBP immune reaction is spread in a large area of the CNS prior to myelin appearance. In addition, for the first time it has been demonstrated that the same population of cells could be labelled with both MBP and macrophage markers. These results indicate that MBP, or MBP-related proteins, could represent a link between the immune and nervous system during early development. Thus, besides the well established role in myelination, these proteins might have an additional and still unknown function in development.