A bacterial lipopolysaccharide (LPS) extracted from a rough strain of Salmonella minnesota ( Re595 ) containing primarily lipid A was used to study tissue distribution following its intravenous injection in rabbits. For this purpose, the Re595 was either labelled with 125iodine (125I) and localization quantitated by gamma radiation spectrometry and radioautography of different tissues or a fluorescein labelled antibody to Re595 was employed. Localization of [125I]- Re595 or LPS was looked for at 30 min and 2 hr after intravenous injection. [131I]-albumin was employed either to measure intravascular protein or total tissue protein and, in some studies, [131I]-albumin and [125I]-fibrinogen were used to measure protein after unlabelled Re595 . Both fractions of isotopes injected and estimates of tissue-bound Re595 were made in the whole eye, liver, spleen, kidney and lung and in isolated iris-ciliary processes, aqueous, lens, vitreous, and posterior segment (retina, choroid, and sclera). Aqueous and iris-ciliary processes, but no other tissues, showed a marked extravazation of [131I]-albumin and [125I]-fibrinogen. [125I]- Re595 was found to localize primarily in liver and spleen. At 30 min, [125I]- Re595 was found in nanogram quantities within the eye and at 2 h greater amounts of LPS were found in iris-ciliary processes and aqueous than in the posterior segment. Neither radioautography nor fluorescein-labelled antibody to Re595 showed evidence of histologic localization of LPS in the iris-ciliary processes. These results indicate that although LPS does not localize preferentially in the eye, it does accumulate in quantities sufficient to have an effect locally.