A controlled crossover feeding study was conducted in eight males aged 20-36 y to compare the effects of skim milk and whole milk on blood lipids. For 6-wk diet periods, 236 mL/4191 kJ of skim or whole milk was consumed with a background diet designed according to the American Heart Association recommendations. Plasma lipids were analyzed at baseline and at 3 and 6 wk. After 6 wk, the mean total cholesterol concentration was 4.47 mmol/L with skim milk and 4.80 mmol/L with whole milk (P < or = 0.001); mean low-density-lipoprotein-cholesterol concentrations were 2.64 and 2.96 mmol/L, respectively (P < or = 0.001). Mean apolipoprotein B decreased with skim milk and increased with whole milk (P < or = 0.05). No statistically significant differences were observed for plasma high-density lipoprotein-cholesterol, triglyceride, apolipoprotein A-I, or fatty acids. Substitution of skim milk for whole milk may decrease the risk of coronary heart disease.