Two studies to investigate the penetration of the aldose reductase inhibitor, Sorbinil, were conducted. In the first study, 24 diabetic patients undergoing intracapsular extraction were randomised into three groups on a double masked basis. In the week immediately preceding the operation, all patients were requested to take two capsules daily before breakfast. Each capsule contained 200 mg Sorbinil, 100 mg Sorbinil, or a placebo. On measuring Sorbinil levels in lens, plasma and erythrocytes using HPLC, three clearly defined groups of patients were obtained. In one group no Sorbinil was detected, in the second group there were moderate levels of Sorbinil, while the third group had significantly higher levels of Sorbinil. The ratio of erythrocyte/plasma Sorbinil was 0.225, while the ratio for lens/plasma was 0.7, for both groups where Sorbinil was detected. In a second study, 20 patients were treated topically with a single dose of 0.5 mg ophthalmic Sorbinil at times ranging from 0-14 hr preoperatively. Sorbinil was detected in both lens and aqueous. Transport into the lens was complete within about 2 hr, and although aqueous levels were negligible after 6 hr, Sorbinil persisted up to 14 hr in the lens. Three out of 16 patients taking Sorbinil orally developed a maculopapular rash with pyrexia approximately 8 days after commencing the drug. No side effects were noted in any patients given the topical ophthalmic preparation.