Cimetidine, a histamine H2 receptor antagonist, is known to have some effects on central nervous system, and is reported to emerge in the cerebrospinal fluid (CSF). We evaluated the elimination of cimetidine from CSF by the method of ventriculo-cisternal perfusion in rats. The extraction ratio of cimetidine at the low perfusate concentration (14 nM) was 0.190 +/- 0.023 (n = 3), while that significantly (p less than 0.02) decreased to 0.0916 +/- 0.081 (n = 3) at the high concentration (4 mM). No significant difference was observed in the production rate of CSF between these two concentrations. These findings suggest that cimetidine is excreted from CSF to blood by a saturable transport system.