Plasma lipid and lipoprotein levels are influenced by physiologic changes during the life span of mammalian organisms. In the present study, the effects of aging and gender on plasma lipids and lipoprotein cholesterol fractions in heterozygous Watanabe heritable hyperlipidemic (WHHL-Hh) rabbits were examined. For 3 years the rabbits were fed regular rabbit chow and were free from any experimental manipulation. Male WHHL-Hh rabbits (n = 17) had a 55% increase in total plasma cholesterol level (p < 0.005) between the ages of 7.5 and 34 months. This increase was due to significant increases in very low-density lipoprotein cholesterol (VLDL-C) (28%, p < 0.05), in low-density lipoprotein cholesterol (126%, p < 0.005), and in high-density lipoprotein cholesterol (28%, p < 0.05). Female WHHL-Hh rabbits (n = 11) did not show significant differences in lipid plasma values with aging. However, their plasma values, with the exception of the VLDL-C, were significantly (p < 0.05) higher than those of the male rabbits. Pregnancy and increased weight in the older female rabbits may have accounted for these differences. Significant plasma lipid changes occur as a function of heterozygosity, age, and gender in WHHL-Hh rabbits. The lipoprotein changes seen in male but not in female WHHL-Hh rabbits during the aging process are similar to those observed in human subjects. Pregnancy in WHHL-Hh rabbits, like in human beings, may induce hyperlipidemia, which is opposite to the effects observed in normal rabbits or homozygous WHHL rabbits.