How weight loss improves lipid levels is poorly understood. Cross-sectional studies have suggested that accumulation of fat in intra-abdominal stores (IAF) may lead to abnormal lipid levels, increased hepatic lipase (HL) activity, and smaller low density lipoprotein (LDL) particle size. To determine what effect loss of IAF would have on lipid parameters, 21 healthy older men underwent diet-induced weight loss. During a period of weight stability before and after weight loss, subjects underwent studies of body composition, lipids, measurement of postheparin lipoprotein and HL lipase activities, cholesteryl ester transfer protein activity, and insulin sensitivity (Si). After an average weight loss of 10%, reductions in fat mass, IAF, and abdominal s.c. fat were seen, accompanied by reductions in levels of triglyceride, very low density lipoprotein cholesterol, apolipoprotein B, and HL activity. High density lipoprotein-2 cholesterol and Si increased. In those subjects with pattern B LDL at baseline, LDL particle size increased. Cholesteryl ester transfer protein activity did not change. Changes in IAF and Si correlated with a decrease in HL activity (although not independently of each other). In summary, in men undergoing diet-induced weight loss, only loss of IAF was found to be associated with a reduction in HL, which is associated with beneficial effects on lipid levels.