Nicotine's affinity for melanin-containing tissues may result from its precursor function in melanin synthesis or the irreversible binding of melanin and nicotine. The objective of this study was to investigate a hypothesized association of tobacco use, dependence, and nicotine exposure with melanin pigmentation among African American smokers. A criterion-based sample was employed to collect data from a study of 147 adult African American current smokers. Carbon monoxide, saliva cotinine samples, and skin reflectance measures were obtained from each participant. Questionnaire data on demographic, sociological and behavioral questions related to smoking and skin color were gathered. The three dependent measures were the average number of cigarettes per day (CPD), Fagerström Test of Nicotine Dependence (FTND) score, and cotinine concentration. Analysis of variance, Pearson Correlations, and Multiple Linear Regression were conducted to analyze findings. The mean constitutive melanin reading was 56.3 and 66.5 for facultative melanin. Respondents on average smoked 19 CPD, had a mean FTND of 5.6, and a cotinine concentration of 435 ng/ml. Facultative melanin level was correlated with CPD and cotinine concentration in the bivariate analysis. The multiple linear regression results revealed that facultative melanin was significantly and positively related to CPD, the FTND, and cotinine. The results of this analysis support the hypothesis of a positive association between melanin levels and tobacco use, dependence, and exposure among African American smokers. This analysis may have important implications for research and interventions on tobacco dependence and disease outcomes. Further research on melanin and nicotine among African Americans as well as other population groups is warranted.