Study Objective Physiological states of estrogen deficiency can lead to bone demineralization. Lead is stored in bone and may be released into blood during demineralization. The contraceptive injection depomedroxyprogesterone acetate (DMPA) is associated with estrogen deficiency and bone demineralization and, we hypothesized, may be associated with toxic blood lead levels in adolescents at high risk for lead exposure. We sought to compare blood lead levels in inner-city adolescent girls using DMPA with levels in those using oral contraceptive pills (OCP) and those taking no hormones and to examine the influence of lead exposure and reproductive history on blood lead levels in the total sample. Design Cross-sectional survey of a clinical convenience sample. Setting Inner-city adolescent clinic in an academic medical center. Participants 174 females aged 13–21 years; 86% minority ethnicity. Interventions None Main Outcome Measures Measurement of blood lead levels and an 82-item questionnaire examining lead exposure and reproductive history. Results 28 subjects were using DMPA, 25 used OCPs, and 121 used no hormones. Mean blood lead level in the total sample of 174 was 1.6 μg/dL, SD = 1.1. Many subjects had environmental risk factors for lead exposure and 15% reported one or more past pregnancies. Mean blood lead levels for subjects with the various environmental and reproductive risk factors ranged from 1.2 μg/dL to 2.0 μg/dL and were not different from levels for subjects without such risk factors. Mean blood lead levels for subjects in the 3 hormonal groups were significantly different (2.1 vs. 1.2 vs.1.5 μg/dL in DMPA, OCP, and no hormone groups respectively, P = 0.007). We dichotomized the blood lead levels into “High” ≥4 μg/dL, or “Low” <4 μg/dL. We found that a significantly higher proportion of girls using DMPA (4/28) than those not using any hormone (2/121) had “High” levels ( P = 0.012). Conclusions Despite reported high-risk exposure to lead and the possibility of long-term accumulation of lead in bone, we did not find elevated blood levels in our sample. However, DMPA-treated girls were significantly more likely to have higher mean blood lead levels than OCP users and non-hormone users. In addition, DMPA users were more likely to have blood lead levels more than two standard deviations above the mean for the sample as a whole than untreated girls. Further studies are needed to examine low-level lead poisoning in adolescents and the consequences of contraceptive choices on bone health.