To define the relationship between apoprotein levels and plasma cholesterol concentration in dogs, we measured the cholesterol, apo B, apo E, apo A-IV, and apo A-I levels in 6 dogs fed a synthetic diet (Diet I), and in 5 dogs fed dog chow supplemented with lard, cholesterol, bile salts, and propylthiouracil (Diet II). The diet-induced hypercholesterolemia exceeded 900 mg/dl in dogs fed Diet I and was accompanied by a 12-fold increase in apo B, a 30-fold increase in apo E, an 8-fold increase in apo A-IV, and a 1 1/2-fold increase in apo A-I. By contrast, the hypercholesterolemia averaged 1300 mg/dl in dogs fed Diet II and was accompanied by a 12-fold increase in apo B, an 11-fold increase in apo E, a 3-fold increase in apo A-IV, and a 5-fold decrease in apo A-I levels. When 3 of the Diet I dogs were switched to dog chow, their plasma cholesterol, apo B, and apo E levels dropped to 30% of their peak value within 7 days. The change in apo B and apo E levels was found to be highly correlated with the change in plasma cholesterol concentrations in each of the Diet I animals (r2 ranged from 0.92 to 0.99 for both apoproteins). A strong linear relationship was also observed between apo E and apo B (r2 ranged from 0.94 to 0.98), indicating that the plasma apo E to apo B ratio remained constant in these animals as the hypercholesterolemia progressed or regressed.