There is growing evidence that several chronic adult diseases, such as coronary heart disease and stroke, can result from events occurring in fetal life. The aim of this study was to examine the relation between birthweight and all-cause mortality in young adults. We studied total mortality in a population-based cohort of 80 936 offspring born in Jerusalem in 1964–76. During an average follow-up of 28.8 years 2 324 984 person-years were contributed and 2092 deaths occurred. Overall, in both genders, the univariable and the multivariable Cox-proportional hazard models indicated a strong negative relationship between birthweight and total mortality, mostly because of infant deaths. At ages 1–14 birthweight seemed unrelated to all-cause mortality. In males aged 15+, birthweight was again a significant predictor of death (Hazard ratio (HR) = 0.88, 95% confidence interval (CI) [0.78, 0.99], for 1 standard deviation (SD) increase in birthweight). The analysis by categories suggested a general decreasing of the risk of mortality with increasing birthweight (HRs = 1.0, 1.02, 0.85, 0.77, 0.57 for those belonging to birthweight groups of < 2500 g, 2500–2999 g, 3000–3499 g, 3500–3999 g and ≥ 4000 g, respectively). In females aged 15+ there was a J-shaped relation between birthweight and mortality but these associations were not statistically significant. These findings add to a growing body of evidence that events during intrauterine life have remote consequences for adult health and underline the need to consider gender differences.