The fasting plasma lipid and lipoprotein levels were measured prospectively in 41 consecutive patients with xanthelasma seen over a four-year period. The study group included 25 women and 16 men with mean ages of 60 and 56 years, respectively. Each patient had clinical evaluation for medications or illnesses that might affect plasma lipid levels before entry into the study. The most striking lipid abnormality was the preponderance of decreased levels of high-density lipoprotein cholesterol (HDL-C). In 94% of the study population, HDL-C values were less than the mean values of the age-matched reference population. For men the mean HDL-C level was 30.8 mg/dl (vs 45 mg/dl in the reference population, P less than .001); for women the mean HDL-C level was 33 mg/dl (vs 50 mg/dl, P less than .001). The total cholesterol, low-density lipoprotein, and triglyceride levels of those in the study were not significantly different from those of the patients in the reference population. Evaluation of cardiac risk based solely on HDL-C levels showed 80% of the study population to have three to four times the average risk. This study points out the high probability of decreased HDL-C levels in patients with xanthelasma. Since the level of HDL-C has been shown to be inversely related to the incidence of cardiovascular disease, it may be prudent to evaluate HDL-C levels and do a thorough cardiovascular evaluation in patients with xanthelasma.