Plasma high-density lipoprotein cholesterol (HDL-C) concentrations are regulated by plasma cholesteryl ester transfer protein (CETP) in humans. The aim of this study was to ascertain the relationship between plasma HDL-C and plasma CETP activities in mouse, rat, dog, hamster, rabbit and monkey. In this study, the plasma HDL-C levels were highest in dogs and lowest in rabbits among the six species. Plasma CETP activities were higher in hamsters, rabbits and monkeys compared to mice, rats and dogs. The present study shows that there are species differences in HDL-C and CETP activity in six species of healthy experimental animals, with the six species being separated into two types. The first type showed a high HDL-C/TC ratio with low or absent CETP activity, and included mouse, rat and dog, whereas the second type showed a low HDL-C/TC ratio and high CETP activity, and included hamster, rabbit and monkey. The present study also shows that there is a strong relationship between plasma HDL-C levels and CETP activity in high CETP activity animals and that the relationship between the HDL-C/TC ratio and CETP activity is an important factor in all animals, regardless of CETP activity level.