The earliest occurrence of macrophages was investigated in the brain and optic anlagen of the tree shrew Tupaia belangeri. Nineteen serially sectioned embryos, belonging to five phases of programmed neuroepithelial cell death previously found during optic cup formation, were used. Macrophages were identified by structural criteria and by labelling with the lectin Griffonia simplicifolia I-B(4). Macrophages, most probably derived from the yolk sac, are present in the perineural vessels of the phase 1 embryo (V-shaped optic evagination). Within this compartment, their number increases up to phase 4 (advanced invagination) and drops during phase 5. This first wave of macrophages is followed by a second one occurring within the perineural mesenchyme and within the neuroepithelium of the brain and eyes from phase 3 onwards. In the phase 4 embryos, a considerable rise in the number of intraventricular macrophages is noted. During phase 5 (far advanced invagination), marked vascularization of the brain starts, and a peak of macrophages is noted in the neuroepithelium and in the ventricular lumen of the brain. This spatiotemporal pattern suggests that, in Tupaia, the earliest macrophages are simultaneously shifted from perineural vessels into the neuroepithelial walls of the developing brain and, at earlier stages than previously described in other vertebrate species, of the eye anlagen.