In the present study rat sciatic nerves (n = 60) were transected; in half of the animals nerve was allowed to regenerate freely, in the other half the regeneration was prevented by suturing beside the point of transection. Macrophages were stained with ED-1 antibody and counted (number/mm2) in both the epi- and endoneurium 3, 7, 14, 48 and 56 days post transection. Macrophages were observed first in the epineurium; the local density of macrophages was considerably higher in the epineurium than in the endoneurium during the first few days. The number of macrophages in the epineurium was maximal at 3 days (1,000-2,000/mm2), and thereafter it declined sharply. In the endoneurium macrophages were most abundant after 2 weeks (1,000/mm2), after which their number declined steadily. A migration of epineurial macrophages appeared to take place through the perineurium from epineurial areas containing a high concentration of macrophages. Initially an endoneurial accumulation of macrophages was noted in the subperineurial area. These findings suggest an alternative route for macrophages into the endoneurial space. No statistical difference was observed between the regenerating and non-regenerating experimental groups. The present study indicates that regenerating axons do not have an effect on the number of macrophages in either the epineurium or the endoneurium.