Peripheral lymph lipoproteins were studied in four hyperlipidaemic men before and after 6 weeks of treatment with gemfibrozil, a drug which is known to increase the fractional catabolic rate of very low density lipoproteins (VLDL) by raising lipoprotein lipase activity in peripheral tissues. Decreases in plasma triglycerides of 18-60% (mean, 45%) were accompanied by increases in lymph apolipoprotein (apo) A-I concentration of 30-108% (mean, 66%; P < 0.01), and in lymph cholesterol concentration of 35-100% (mean, 59%; P < 0.05). The additional lymph cholesterol was distributed over a broad range of lipoprotein particle sizes. Effects on plasma apo A-I concentration (mean, +7%) and plasma total cholesterol concentration (-7%) were not statistically significant. No changes were observed in four untreated control subjects. These findings are compatible with the hypothesis that lipolysis of VLDL at the blood-endothelium interface increases the transfer of apo A-I from plasma to interstitial fluids, and thereby promotes cholesterol efflux from cells.