We examined the relation between low birth weight and childhood family and neighborhood socioeconomic disadvantage and disease onset in adulthood. METHODS: Using US nationally representative longitudinal data, we estimated hazard models of the onset of asthma, hypertension, diabetes, and stroke, heart attack, or heart disease. The sample contained 4387 children who were members of the Panel Study of Income Dynamics in 1968; they were followed up to 2007, when they were aged 39 to 56 years. Our research design included sibling comparisons of disease onset among siblings with different birth weights. RESULTS: The odds ratios of having asthma, hypertension, diabetes, and stroke, heart attack, or heart disease by age 50 years for low-birth weight babies vs others were 1.64 (P < .01), 1.51 (P < .01), 2.09 (P < .01), and 2.16 (P < .01), respectively. Adult disease prevalence differed substantially by childhood socioeconomic status (SES). After accounting for childhood socioeconomic factors, we found a substantial hazard ratio of disease onset associated with low birth weight, which persisted for sibling comparisons. CONCLUSIONS: Childhood SES is strongly associated with the onset of chronic disease in adulthood. Low birth weight plays an important role in disease onset; this relation persists after an array of childhood socioeconomic factors is accounted for.