The receptiveness of the brain to monocyte infiltration was studied in rats that had been injected intracerebrally with Corynebacterium parvum. At 0-17 days after intracerebral injection and 18 h after intravenous injection of diI-labeled isogenous mononuclear cells, host rats were sacrificed and cells from the vicinity of the injection site and from the contralateral cerebral hemisphere were dissociated and analyzed by flow cytometry. In rats sacrificed 4-11 days postinjection of C. parvum, diI-labeled mononuclear cells were detected in cell preparations from the hemisphere ipsilateral and, to a lesser extent, contralateral to the injection site. No extravasation of cells from the blood to the brain was detected in rats injected intracerebrally with saline. By immunohistochemistry, many macrophages were detected in the hemisphere ipsilateral to injection of C. parvum. In additional experiments, the dissociated CNS cell population was labeled with OX-42 antibodies to the type 3 complement receptor, which is present on monocytes but not lymphocytes. Some cells in the brain were labeled with both diI and OX-42 and therefore were identified as monocytes that had entered the brain from the blood. In conclusion, monocytes can home to both sides of the brain after unilateral injection of a strong inflammatory agent but monocyte infiltration into the brain is delayed in comparison to monocyte inflammatory responses that have been reported in nonneural tissues.