The purpose of this study was to examine relationships between aerobic fitness and birthweight in adolescents. A representative cohort of 1015 males and females aged 12 and 15 y was studied, at baseline, with 89% of the 12-y-olds being re-examined 3 y later. The main outcome measures were an index of aerobic fitness, measured in laps completed at voluntary exhaustion by a twenty-metre shuttle run test, and recorded birthweight. Multiple linear regression, with and without adjustment for known and potential confounding variables, was performed to examine associations between fitness and birthweight. Birthweight and aerobic fitness were positively related so that for each kg decrease in birthweight, there was a mean (95% confidence interval) decrease in fitness score of 4.84 (0.35 to 9.33) laps and 3.21 (0.32 to 6.10) laps, in 12-y-old boys and girls respectively. This relationship is of a similar order to the strength of association between birthweight and adult blood pressure previously reported. Associations between birthweight and physical fitness at the age of 15 were weaker and were not significant. Our findings suggest that aerobic fitness may be involved in mediating the association between birthweight and cardiovascular disease risk later in life. The weakening of the association between birthweight and fitness between the ages of 12 and 15 y is similar to the weaker associations between birthweight and blood pressure seen among adolescents compared to younger children. We are currently re-examining this cohort to see if, as with blood pressure, the association with fitness re-emerges at an older age.