The phagocytic cells in the rat olfactory epithelium were examined after unilateral bulbectomy. Immunohistochemistry using a monoclonal anti-macrophage antibody (OX42) and electron microscopy showed that macrophages were present in the olfactory epithelium of the operated side 1 day after bulbectomy. The average number was 5.9 OX42-positive cells/2 mm septal epithelium, compared with 2.9 in unoperated controls. At 3 days the number of macrophages/2 mm epithelium peaked at 16 and subsequently dropped to 2.1 at 7 days. The number of macrophages and the timing of their appearance in the olfactory epithelium during the 1st week after bulbectomy were related to the acute and massive death of olfactory cells. The number of macrophages returned to control levels at longer postoperative times (14, 30, 60, and 90 days). Most of the OX42-positive macrophages were the ED1-positive activated type. At 6 and 7 days after surgery large phagosomes containing cell debris were observed in the cytoplasm of supporting cells in the epithelium. The phagocytosis by supporting cells was more evident at 30, 60, and 90 days, in the chronic stages of cell death. The results indicate that macrophages are the major phagocyte in the olfactory epithelium during the 1st week after bulbectomy and that both supporting cells and macrophages participate in phagocytosis at longer survival times.