This study evaluated lung cancer risk in 2,977 first-degree relatives of 565 patients in whom lung cancer had been diagnosed prior to age 50 years from the Surveillance, Epidemiology, and End Results (or SEER) program registry in metropolitan Detroit and compared it with the risk among 3,421 relatives of 715 population-based control subjects under the age of 50 years, who had been identified through random digit telephone dialing. After adjusting for age, race, sex, and pack-years of smoking in generalized estimating equation models, the relatives of patients had a 2.6 times greater risk of developing lung cancer than did the relatives of control subjects (95% confidence interval, 1.8 to 3.8). African-American (AA) case relatives were at a 4.3-fold risk compared to AA control family members (95% confidence interval, 2.2 to 8.5). The cumulative incidence of lung cancer development among relatives was examined using Kaplan-Meier survival curves. By age 70 years, 11.1% of AA smokers with a family history developed lung cancer, compared to 2.7% of AA smokers without a family history. In whites, 4% of smokers with a family history of lung cancer developed lung cancer, compared to 2.2% of smokers without a family history. When pack-years and family history of early-onset lung cancer were considered, heavy smokers (ie, > 33 pack-years) with a family history of lung cancer had a 6.7% risk of developing lung cancer by age 70 years, while those without a family history had a 2.9% risk of developing lung cancer. These findings provide support for the familial aggregation of lung cancer and the role of gene-environment interactions in lung cancer, and they underscore the need for the continuation of studies of genetic susceptibility that include AAs.