Earlier work with human subjects showed that a low-fat, low-cholesterol diet lowered plasma high-density-lipoprotein-cholesterol (HDL-C) and the production rate of apolipoprotein A-I (apo A-I). More recent research with transgenic mice demonstrated that a high-fat, high-cholesterol diet raised plasma HDL-C and the production rate of apo A-I by a mechanism involving the regulation of translation of the apo A-I mRNA. The authors conclude that the rise induced in HDL-C by a high-fat, high-cholesterol diet is defensive and therefore, should not be interpreted as a desirable dietary change.