Osteoporotic fractures (OFs) are a major public health problem. Direct evidence of the importance and, particularly, the magnitude of genetic determination of OF per se is essentially nonexistent. Colles' fractures (CFs) are a common type of OF. In a metropolitan white female population in the midwestern United States, we found significant genetic determination of CF. The prevalence (K) of CF is, respectively, 11.8% (6SE 0.7%) in 2471 proband women aged 65.55 years (0.21), 4.4% (0.3%) in 3803 sisters of the probands, and 14.6% (0.7%) in their mothers. The recurrence risk (K0), the probability that a woman will suffer CF if her mother has suffered CF is 0.155 (0.017). The recurrence risk (Ks), the probability that a sister of a proband woman will suffer CF given that her proband sister has suffered CF is 0.084 (0.012). The relative risk l (the ratio of the recurrence risk to K), which measures the degree of genetic determination of complex diseases such as CF, is 1.312 (0.145;λo) for a woman with an affected mother and 1.885 (0.276;λs) for a woman with an affected sister. A l-value significantly greater than 1.0 indicates genetic determination of CF. The terms l0 and ls are related to the genetic variances of CF. These parameters translate into a significant and moderately high heritability (0.254 [0.118]) for CF. These parameters were estimated by a maximum likelihood method that we developed, which provides a general tool for characterizing genetic determination of complex diseases. In addition, we found that women without CF had significantly higher bone mass (adjusted for important covariates such as age, weight, etc.) than women with CF. (J Bone Miner Res 2000;15:1243-1252)