Subarachnoidal application of the complement C5a fragment was used to induce acute experimental meningitis in rabbits and rats within 30–60 min. The early stages of the cellular inflammatory response were studied by means of flow cytometry, transmission electron microscopy and immunofluorescence microscopy. Infiltration of polymorphonuclear leukocytes (PMN) into the subarachnoidal space was the earliest event of the inflammatory reaction. By morphological criteria we found that PMN interacted with cells of the mononuclear-macrophage lineage (MML) and the marginal astrocytes via pseudopodia, whereas the pial cells were not involved in early stages of the inflammatory response. The number of invaded MML that were positive with the ED2 marker increased, indicating the hematogenous origin of the immigrating cell population. PMN were found to infiltrate the perivascular space of the marginal arterial vessel segments. This perivascular infiltration was assumed to be the first manifestation of cerebral vasculitis. The intimate association of resident cerebral cells (astrocytes) with invading PMN and MML is suggestive of a transient interaction of these cell types.