The effects of nicardipine hydrochloride (NH), a calcium channel blocker, on the intraocular pressure (IOP) and aqueous humor dynamics were studied in the rabbit eye. Thirty micrograms/kg of NH administered intravenously by bolus injection into an ear vein significantly lowered IOP for 5 to 30 minutes. But topical administration of NH significantly increased IOP, as compared with the fellow control eye at 15 and 30 minutes. This increased IOP was a dose-dependent response; the maximum effect was 4.3 +/- 0.6 mmHg at 15 minutes after administration of 0.1%NH. Severe hyperemia was observed at the limbus for 3 hours after topical administration. The aqueous flow rate after topical application of 0.1%NH showed no significant difference between treated and fellow control eye. However, the coefficient of aqueous outflow after topical application of 0.1%NH was significantly decreased (0.08 +/- 0.01 microliters/min/mmHg: p < 0.05) as compared with fellow control eye (0.13 +/- 0.02 microliters/min/mmHg). The penetration level of 0.1%NH into the aqueous humor of the rabbit eye was 0.22 +/- 0.13 micrograms/ml, 30 minutes after topical administration. Systemic NH decreased IOP, but topical NH increased IOP by increasing resistance of aqueous outflow.