Utilizing the polyvinyl sponge-implant model in the rabbit we have previously demonstrated modification in low density lipoproteins (LDL) of interstitial tissue fluid obtained in association with a cellular inflammatory response. In order to examine the interaction between the inflammatory response and lipoproteins from hypercholesterolemic rabbits, 30 male, New Zealand White rabbits were fed standard chow supplemented with 0.5% cholesterol for 4 weeks prior to sponge implantation. Lipoproteins were prepared from interstitial inflammatory fluid (IF) as well as homologous whole plasma (WP). Total IF cholesterol was positively correlated with plasma cholesterol (459 ± 43 vs. 1485 ± 130 mg/dl, X ± SEM, r = 0.81, P < 0.01). Distribution of lipoproteins in IF was similar to WP in both particle size and density. Beta-migrating VLDL were the predominant particles in both WP and IF, containing 43.7 ± 3.4 and 42.2 ± 5.1% of WP and IF cholesterol, respectively. IF-VLDL were similar to WP-VLDL in lipid and apoprotein composition, morphology and particle size distribution. We conclude from these data that the observed dramatic alterations in lipoprotein distribution in response to a dietary cholesterol challenge in rabbit plasma is essentially unaltered in interstitial inflammatory fluid obtained from these animals.