High smoking prevalence and low quit smoking rates among African American adults are well-documented, but poorly understood. We tested a transdisciplinary theoretical model of psychopharmacological-social mechanisms underlying smoking among African American adults. This model proposes that nicotine's acute attention-filtering effects may enhance smoking's addictiveness in populations unduly exposed to discrimination, like African American adults, because nicotine reduces the extent to which discrimination-related stimuli capture attention, and in turn, generate distress. During nicotine deprivation, attentional biases toward discrimination may be unmasked and exacerbated, which may induce distress and perpetuate smoking. To test this model, this within-subject laboratory experiment determined whether attentional bias toward racial discrimination stimuli was amplified by nicotine deprivation in African American adults who smoked daily. Participants (N = 344) completed a computerized modified Stroop task assessing attentional interference from racial discrimination-related words during two counterbalanced sessions (nicotine sated vs. overnight nicotine deprived). The task required participants to quickly name the color of discrimination and matched neutral words. Word Type (Discrimination vs. Neutral) × Pharmacological State (Nicotine Deprived vs. Sated) effects on color naming reaction times were examined. Attentional bias toward racial discrimination-related stimuli was amplified in nicotine deprived (reaction time to discrimination minus neutral stimuli: M [95%CI] = 34.69 [29.62, 39.76] ms; d = 0.15) compared to sated (M [95%CI] = 24.88 [19.84, 29.91] ms; d = 0.11) conditions (Word Type × Pharmacological State, p < .0001). The impact of nicotine deprivation on attentional processes in the context of adverse societal conditions merit consideration in future science and intervention addressing smoking in African American adults. (PsycInfo Database Record (c) 2023 APA, all rights reserved).