While a wide variety of techniques has been used to collect samples of interstitial fluid, most of our detailed knowledge about the composition of interstitial fluid lipoproteins has come from lymph collection studies. The considerable variability of lymph data probably reflects the effect of variable metabolic modification and different capillary permeabilities on the lipoprotein composition of interstitial fluid. All density classes of plasma lipoproteins are present in lymph. In peripheral lymph, the lymph/plasma concentration ratios of lipoproteins vary from 0.03 for VLDL-sized particles to 0.2 for HDL. Lymph from more permeable vascular beds, such as lung and myocardium, contains proportionately more lipoproteins. Their lymph/plasma concentration ratios vary from 0.1 to 0.6. In general, lymph lipoproteins are more heterogeneous in size than their plasma counterparts. Lymph HDL and LDL contain larger and smaller particles than their plasma equivalents. Lymph lipoproteins have unusual shapes (square packing and discoidal), chemical compositions, and molecular charge, which suggest de novo formation and/or extensive peripheral modification. Lymph HDL and LDL are enriched in free cholesterol. Lymph HDL also has increased cholesterol/protein and phospholipid/protein (especially sphingomyelin) ratios (Sloop, C.H., L. Dory, and P.S. Roheim, unpublished observations). Lymph HDL apoprotein composition differs from that of plasma, with an increase in apoE and apoA-IV content relative to apoA-I. These discoidal HDL particles may be products of an initial stage of reverse cholesterol transport. We believe further study of their metabolic fate would give important information concerning the later stages of reverse cholesterol transport.