To study the effect of hyperlipidemia on vascular permeability, serial anterior chamber fluorophotometric examinations were carried out on 33 control rabbits (group 1) and 32 diet-induced hypercholesterolemic (group 2) rabbits. Changes in the blood-aqueous barrier function associated with total serum cholesterol (CHO) and triglyceride (TG) levels were studied at the beginning of the study and every 2 weeks thereafter for up to 16 weeks following 0.5% cholesterol-enriched diet feeding. Concurrently, a slit-lamp biomicroscope was used to examine the iris for evidence of atheromatous plaque. In group 1, the CHO level decreased slightly during the first 6 weeks and remained rather steady thereafter. The status of the blood-aqueous barrier correlated significantly with serum CHO and TG levels (r = .46, P < .001; r = .23, P = .01, respectively). In group 2, CHO and TG levels increased significantly after 2 and 8 weeks of cholesterol-enriched diet feeding, respectively. The blood-aqueous barrier also became more permeable than that in group 1 after 2 weeks' and increased above its baseline level after 6 weeks' feeding. Both CHO and TG levels correlated well with the degree of blood-aqueous barrier breakdown (r = .51, P < .001; r = .25, P < .001, respectively). The first evidence of iridic lipid-streak deposition was noted at 7.6 +/- 0.7 weeks, while definite iridic atheromatous plaque appeared 11.2 +/- 0.7 weeks after feeding. The change in the blood-aqueous barrier also correlated well with the semiquantitative score of iridic plaque (r = .58, P < .001) and usually preceded visual evidence of plaque formation.(ABSTRACT TRUNCATED AT 250 WORDS)