From a group of 53 rhesus monkeys, we selected 12 animals, the six with the highest and the six with the lowest response to a high cholesterol diet, and we made detailed analyses of their cholesterol and apolipoprotein profile. The high responders differed from the low responders in several ways. During the high cholesterol diet period, the high responders had much higher plasma apolipoprotein B and E concentrations and much lower plasma apolipoprotein A-I concentrations than did the low responders. Nearly all the increase in plasma cholesterol and apolipoproteins B and E concentrations in the high responders occurred in the lower density fractions (d = 1.006-1.030 g/ml), while the decrease in plasma apolipoprotein A-I concentrations in the high responders was confined to the lower density fraction of the high density lipoproteins (HDL), i.e., HDL2 (d = 1.063-1.125 g/ml). In the low responders, on the other hand, the slight increase in cholesterol concentrations was evenly distributed between the lower density fractions and HDL, and the increase in apolipoprotein A-I concentration of the lower density fractions is related to the decrease in the concentration in the HDL2 in the high responders.