Since 1985, we prospectively followed 246 patients with ALS. The relationship between the age of developing neurological impairment and disease duration was analyzed in 138 patients (86 men and 52 women) who died. Mean disease duration was 4.0 +/- 3.8 years for men and 3.2 +/- 2.5 years for women. There was an inverse, exponential, relationship between onset age and duration (goodness-of-fit P > 0.05). Mean duration at onset age < or = 40 years was 8.2 +/- 5.0 years compared with 2.6 +/- 1.4 years for patients aged 61 to 70 years (P > 0.001). The ratio of young (< or = 40 years) men to women was 3.6:1. When matched for age, disease duration was the same for patients with bulbar and nonbulbar onsets. We conclude that onset age, but not sex, is the most significant predictor determining disease duration in ALS. Longer survival in younger patients probably reflects their greater neuronal reserve.