Cerebrovascular permeability to protein (CVP-p) was assessed in rats following the systemic injection of either kainic acid (KA) or harmaline. The extravasation of a foreign (horseradish peroxidase, HRP) or an endogenous (rat immunoglobulin G, IgG) tracer protein was determined using immunohistochemical methods. During KA-induced seizures, an extravasation of both HRP and presumed IgG occurred in similar forebrain loci; a lamina-specific extravasation occurred within the dorsal hippocampus. During harmaline-induced tremors protein extravasation also occurred, but was tracer dependent. HRP reaction product was observed within the inferior olive, the cortex of the cerebellar vermis and the neocortex. However, IgG-like immunoreactivity was only detected within the circumventricular organs of harmaline-treated rats. Because KA, but not harmaline, is neurotoxic, the results are consistent with an influence of endogenous serum protein extravasation on seizure-related hippocampal damage. Possible homeostatic properties of altered CVP-p are also considered.