Local application of hydralazine has been found to alter intraocular pressure in animal eyes. This study was undertaken to determine, in normotensive humans, the effects of topically-applied hydralazine on systemic cardiovascular parameters, blood-aqueous barrier, and aqueous humor flow. Two different concentrations of hydralazine were used: 0.03%, and 0.1%. Twenty healthy normotensive subjects were studied. Blood pressure, pulse rate, and intraocular pressure were measured every hour for six hours after hydralazine or placebo was instilled into the conjunctival sac in a double-masked, randomized fashion. With either hydralazine dose, there was no significant change in systemic blood pressure or pulse. In addition, spectrophotometrically-measured polarization of fluorescence and flare failed to show any significant breakdown of the blood-aqueous barrier. In most individuals, application of hydralazine was followed by a brief, mild to moderate, conjunctival hyperemic response. Compared to placebo at the same time of day, a small increase in intraocular pressure was observed with 0.03% hydralazine (p < .05). At 0.1%, this increase tended to be less. There was no statistically significant difference in aqueous humor flow between hydralazine-treated and placebo-treated eyes at the lower concentration (3.20 +/- 0.63 vs. 3.05 +/- 0.61 microL/min (mean +/- S.D.) or at the higher concentration (3.37 +/- 0.53 vs. 3.28 +/- 0.60 microL/min) of hydralazine. These results suggest that acute topical application of 0.1% hydralazine to the eyes of normal humans does not cause clinically significant cardiovascular effects or significant ocular toxicity.