The independent effects of weight loss and dietary fat modification on serum lipids were investigated in two groups of healthy moderately obese men and women. In one group (sequential group, n = 19), a weight-stable low-fat, low-saturated-fat diet (Low-Sat) was given for 7 weeks (= dietary modification), followed by a 4.2 MJ/day deficit Low-Sat diet for 13 weeks (i.e., weight loss alone). Another group (simultaneous group, n = 22) received a 4.2 MJ/day deficit Low-Sat diet for 13 weeks (i.e., weight loss+dietary fat modification). Each group was subject to an initial weight-stable high-fat, high-saturated fat diet for 3 weeks and a final weight stable Low-Sat diet for 3 weeks. Both groups lost similar amounts of body weight, about 13 kg, and had similar overall changes in total cholesterol, low density lipoprotein (LDL), cholesterol, high density lipoprotein (HDL) cholesterol, the HDL/LDL ratio, and triglycerides. Analysis of the separate effects of the Low-Sat diet without energy restriction and of weight loss in the sequential group showed that weight loss per se was responsible for about 50% of the total reduction in total cholesterol, and for about 60% and 70% of the fall in LDL cholesterol and triglycerides, respectively. Fat modification without weight loss reduced HDL cholesterol by 11.1% and the HDL/LDL ratio by 7.7%, while weight loss per se led to increases in HDL cholesterol of 12.5% and in the HDL/LDL ratio of 24.0%. We conclude that the effects of reduction in fat and saturated fat intake and weight loss are additive.(ABSTRACT TRUNCATED AT 250 WORDS)