Healthy 6-8-wk-old New Zealand white rabbits were injected with chromium-chloride- or sodium-chromate-labeled E. coli endotoxin after rapid infusion (10 ml/kg in 1 hr) or slow and repeated infusions (40 ml/kg daily for 7 consecutive days) of 10% Intralipid. Endotoxin clearance rates and RES organ uptakes were determined and the results were compared with those of the controls treated with correspondingly equal volumes of 5% D/W instead of fat. In the acute experiment, the clearance rates were similar in all animals during the first 15 min following endotoxin injection. After this phase, however, experimental animals had faster endotoxin clearance and eventually higher organ uptakes than the controls. In the chronic experiment, there was no significant difference in endotoxin clearance rates or total and per-gram organ uptakes between experimental and corresponding control animals infused with 5% D/W instead of fat. Experimental animals, particularly those having received multiple infusions of fat emulsion, showed deposition of polarizable brown pigment inside and outside the reticuloendothelial cells in the liver, spleen, and bone marrow. None of the controls had these pigments in their organs.