It is well recognized that a favorable lipid profile provides protection from atherosclerotic cardiovascular disease. Because the major cause of nontraumatic death in the western world is considered to be due to cardiovascular disease, centenarians (defined here as subjects over 95 years of age) are believed to possess "atherosclerotic protective" factors. However, it is impossible to study comparatively the lipid profile in centenarians because of lack of controls. Assuming that certain genes responsible for encoding the lipid phenotype may be inherited, we studied the lipid profile characteristics of offspring of centenarians and compared them with control groups. Prospective cohort study. The study was part of the Longevity Genes Project at Albert Einstein College of Medicine. Ashkenazi Jewish centenarians (n = 27, 98.4 +/- 10.4 years) and their offspring (n = 33, 67.4 +/- 1.4 years). The Ashkenazi Jewish offsprings' spouses, who were not related by blood to the centenarians or their offspring, were used as a control group (n = 26, 68.4 +/- 1.2 years). The lipoprotein profile of the offspring was compared with the above control group and to a larger control group (age and gender matched) from the National Health and Nutrition Examination Survey (NHANES) III study (without the sample weights, n = 394, 60 to 69 years). Female offspring of centenarians had significantly higher plasma levels of high density lipoprotein-cholesterol (HDL-C) levels compared with controls (70.2 +/- 3.1 vs 59.0 +/- 4.1 mg/dl, P = .029). Male offspring of centenarians had higher plasma levels of HDL-C levels (56.2 +/- 7.1 vs 44.3 +/- 3.4 mg/dl, P = 0.130) and significantly lower LDL-cholesterol (LDL-C) levels (95.0 +/- 6.0 vs 127.0 +/- 8.0 mg/dl, P = .009) compared with controls. Offspring of centenarians have a favorable lipid profile compared with controls. These data support the notion that a certain phenotypic lipid profile may be transmitted in families and suggest that a favorable lipid profile may play a role in longevity.