Several reports have suggested that modest weight losses, as little as 10% of initial weight, are sufficient to control many of the health complications of obesity. This study examined the relation between changes in weight and those in serum lipids and lipoproteins in obese women who participated in a 48-wk weight-reduction study. Subjects were 66 obese women who were prescribed a 3870-kJ (925-kcal)/d diet for the first 16 wk and a balanced-deficit diet of 5029-6279 kJ (1200-1500 kcal)/d thereafter. Anthropometric measures were assessed at baseline and weeks 8, 24, and 48, as were serum triacylglycerols (triglycerides), total cholesterol, and low-density-lipoprotein- and high-density-lipoprotein-cholesterol concentrations. Weight decreased 11.1% during the first 8 wk, during which time triacylglycerols and total cholesterol fell 22.7% and 15.7%, respectively. Subjects lost an additional 4.7 kg (equal to a total reduction of 16.4%) between weeks 8 and 24 but triacylglycerols and total and low-density-lipoprotein cholesterol increased by 5.2%, 4.2%, and 4.5%, respectively during this time. Multiple-regression analyses showed that at no time did weight loss account for > 6% of the variance in the reductions in triacylglycerol and cholesterol concentrations. These findings indicate that modest weight losses are associated with significant improvements in serum lipids, but that factors including the energy and macronutrient content of the diet prescribed contribute significantly to the improvements observed.