Using prospective data from a community-based sample, the authors tested (a) whether low birth weight (LBW) was a vulnerability marker for children's early drug use and (b) whether the antecedents and sequelae of LBW may act as mediators or confounders in the pathway to early drug use. A total of 823 children and their mothers--473 LBW (<2,500 g) and 350 normal birth weight (NBW)--were assessed when the children were 6 years old and again when they were 11 years old. The incidence of drug use was higher in LBW versus NBW boys (relative odds = 2.0, 95% confidence interval = 1.2-2.6), but there was no difference in incidence for girls. The increased risk for LBW boys remained after adjustment for IQ, externalizing problems, attention-deficit/hyperactivity disorder, and maternal smoking. These findings suggest that LBW is a useful vulnerability marker for early drug use among boys, independent of the antecedents and sequelae of LBW.