To investigate the effect of the terminal complement complex (TCC) on the central nervous system, we injected both the cytolytically active and the inactive complexes into the lateral ventricle of rats. Both complexes promoted accumulation of leukocytes into the cerebrospinal fluid at 4-6 h post-injection. The cells recovered at this time were mostly polymorphonuclear leukocytes (PMN) that were partially replaced by mononuclear cells at 12 h. A direct contribution of the complexes to the in-vivo migration of leukocytes was ruled out by their inability to be chemotactic for rat PMN. Contaminating C5a is unlikely to be responsible for the effect of TCC because it failed to mobilize leukocytes when injected into the lateral ventricle. Histological analysis of rat brains 6 hours after injection of TCC revealed marked leukocyte infiltration of the choroid plexus, increased expression of intercellular adhesion molecule-1 and egression of leukocytes out of the meningeal vessels. The cerebrospinal fluid of rats treated with TCC exhibited chemotactic activity for rat PMN and increased levels of growth related oncogene/cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1 preceding the accumulation of leukocytes. Elevated concentration of IL-1 beta was also found in the cerebrospinal fluid and in periventricular areas of rats treated with TCC.