This study assessed the contribution of genetic and nongenetic factors to biological aging in American Caucasians. The studied sample included 1402 members of 288 pedigrees from the Framingham Heart Study. The original cohort participants received hand radiography in 1967–1969 (mean age, 58.7 years) and their offspring in 1992–1993 (mean age, 51.6 years). An osseographic score was applied to hand radiographs. Standardized residuals between Osseographic Scoring System-predicted age and actual age were used as a measure of biological age (BA). In variance component genetic analysis, sex, cohort, height, body mass index, and, in women, menopausal status and estrogen use, jointly explained approximately 6% of the total variance of BA. Genetic factors explained an additional 57%. Linkage analysis of covariate-adjusted BA suggested the presence of quantitative trait loci on chromosomes 3p, 7q, 11p, 16q, and 21q. In conclusion, the variation in BA measured by radiography was strongly governed by genetic factors in a sample of American adults.