The effect of topical 0.5% timolol on the permeability of the blood-aqueous barrier to plasma protein was studied in ten young normal volunteers. Before and after instillation of timolol in one eye, simultaneous measurements of aqueous flow rate, f(t), by fluorophotometry and protein concentration in the anterior chamber, Ca(t), with a laser flare-cell meter were made in both eyes at hourly intervals. The coefficient of protein entry into the anterior chamber was calculated using an equation formulating protein dynamics in the anterior chamber from the changes in f(t), Ca(t), and plasma protein concentration. The Ca(t) in the treated eye showed a maximum increase of 37 +/- 4% (mean +/- SEM) as compared with that in the fellow eye 5 hours after instillation, while the f(t) in the treated eye showed a maximum reduction of 30 +/- 4% 2 hours after instillation. The intraocular pressure in the treated eye showed a maximum reduction of 3.0 +/- 0.3 mmHg 2 hours after instillation. No significant changes were found in the coefficient of protein entry in the anterior chamber between before and after timolol instillation or between timolol-treated and fellow untreated eyes. These results indicated that topical 0.5% timolol does not affect the permeability of the blood-aqueous barrier to plasma protein significantly.