To ascertain the corneal storage and the possible systemic absorption of 2% cyclosporin-A (CsA) eyedrops, the authors studied, by RIA with monoclonal specific antibodies, the corneal and blood levels of the drug following its topical administration on healthy albino rabbit eyes. When topical CsA was administered following a low-dose application schedule [such as a single dose of 100 microliters every 12 h for 5 days (group 1)], CsA corneal levels of 260.8 +/- 59.8 ng/ml and blood levels of 55.67 +/- 24.4 ng/ml (expressed as means +/- SD) were achieved. These levels significantly increased to 1,111.27 +/- 449.4 ng/ml (p > 0.0001) and 88.66 +/- 59.7 ng/ml (p > 0.05), respectively, when a higher dosage was used [100 microliters every 6 h for 10 days (group 2)]. It is shown that a dose-dependent corneal concentration of CsA, due to a cumulative effect, is achieved in the intact rabbit cornea following topical application of the drug. Systemic absorption of CsA, although irregular, does exist. Therefore, when using topical 2% CsA as in this study, a systemic effect of the drug (especially in low weight animals) should be considered when analyzing the results of topical application.