OBJECTIVE: To assess the relative risk for amyotrophic lateral sclerosis (ALS) in families of ALS patients. METHODS: We conducted a cohort study based on the Swedish Multi-Generation Register in 1961 to 2005. Among 6,671 probands (first ALS case in the family), 1,909 full siblings, 13,947 children, and 5,405 spouses were identified (exposed group). Other persons in the Multi-Generation Register, who were siblings, children, or spouses to persons without ALS, served as the reference group. Relative risks for ALS among the exposed group, compared with the reference group, were calculated from Poisson regression models. Concurrence of ALS within twins was assessed in 86,441 twin pairs registered in the Swedish Twin Register. RESULTS: Nine cases of ALS were noted among the siblings and 37 cases among the children of the probands, giving a 17-fold risk among the siblings (95% confidence interval, 8.1-30.4) and a 9-fold risk among the children (95% confidence interval, 6.2-12.0), compared with the reference group. Siblings and children had a greater excess risk if the proband was diagnosed at a younger age, and the excess risks decreased with increasing age at diagnosis of the proband (p