Effect of a single instillation of 30 microliters 0.5% apraclonidine on the coefficient of protein entry (k(in)), a quantitative index of blood-aqueous barrier permeability, was determined in ten normal volunteers. Before and after administering the drug to one eye and the vehicle to the other eye of a subject, protein concentrations in the anterior chamber were measured using a laser flare-cell meter. One week later, aqueous flow rate was determined by fluorophotometry under the same experimental conditions. The k(in) was calculated from protein concentrations in the anterior chamber and the plasma and from aqueous flow rate based on a transfer equation formulating the kinetics of protein molecules in the anterior chamber. The k(in) showed a significant reduction at 3 and 4 hr after drug administration with a maximum decrease of 21 +/- 6% (mean +/- S.E., n = 10) at 3 hr, while the aqueous flow rate showed a significant reduction from 2 to 6 hr with a maximum decrease of 45 +/- 5% at 3 hr. The results indicated that topical apraclonidine reduced both blood-aqueous barrier permeability as well as aqueous flow rate in humans. This dual reduction may relate to the efficacy of this drug in suppressing the post-laser intraocular pressure rises in patients.