Lead toxicity has been associated with behavioral handicaps, reading disability, antisocial and hyperactive behavior, juvenile delinquency, and impaired cognition. In addition, preclinical studies suggest an association with drug addiction; e.g., animals treated with lead either pre- or postnatally self-administer opiates at a much higher rate than untreated animals. Iron deficiency further increases the risk of lead toxicity through enhanced absorption of lead in the gastrointestinal tract. Female injection drug users have a high prevalence of iron deficiency, although the question remains as to whether this relationship is either a partial function of high lead exposure or heroin use. Specific aims were to preliminarily determine whether female injection heroin users have high tibial lead concentrations, a marker for cumulative lead exposure, compared with normal reference populations, and whether cognitive deficits potentiated the relationship between lead exposure and frequency of heroin use. Tibial lead concentrations were measured via 109 Cd-based K-shell X-ray fluorescence. In 26 female injection heroin users, mean (standard deviation (SD)) tibial lead concentration was 14.5 (6.8) microg/(g bone mineral), which was 1.8 times higher than the tibial lead concentration found among age-adjusted normal community-dwelling women. Interaction effects of tibial lead concentration and selected cognitive functions on frequency with which heroin was used were significant. Further research is warranted to determine whether a history of lead exposure is associated with increased proclivity to drug addiction.