PROJECT SUMMARY/ ABSTRACT Tobacco use remains the single leading preventable cause of death and disability in the United States, accounting for 480,000 deaths and $170 billion in medical costs each year. Although most cigarette smokers eventually want to quit, the majority (80%) are not interested in quitting within the next month. Despite this, smoking cessation treatment programs are traditionally predicated on smokers’ motivations to quit, with treatments proceeding only among those willing to set a quit date. This stands in stark contrast to treatments for other chronic diseases (e.g., hypertension)—health care providers do not assess whether or not patients are ready to treat their high blood pressure, they simply identify the problem and initiate treatment. Tobacco treatment programs are beginning to move toward a similar strategy through population health management approaches; however, there is a dearth of treatment content applicable to smokers across a range of quit- readiness, particularly for those unwilling to set a quit date. One novel potential treatment strategy is to foster practice quitting (PQ), in which an individual attempts not to smoke for a few hours or days, without pressure or expectation to permanently quit. Although a growing body of evidence has supported the role of practice quitting in fostering permanent quit attempts and cessation, there is limited understanding of the mechanisms of PQ-focused treatment. Furthermore, no studies to date have attempted to disentangle treatment effects associated with behavioral vs. pharmacological intervention strategies to prompt practice quitting. The overall goal of the current research is to characterize treatment mediators of PQ-focused counseling and nicotine replacement therapy (NRT) sampling. We will use a 2x2 factorial study design to test the role of PQ counseling vs. Motivational Interviewing (MI) counseling, and NRT sampling (four-week supply of nicotine lozenges and patches) vs. none on incidence of quit attempts at 6-months post treatment. We hypothesize that PQ treatment components will have an additive effect, such that PQ counseling + NRT sampling will produce the highest incidence of quit attempts at 6 months post-treatment. Participants (N=780) will be recruited through a nationwide online recruitment strategy and all study procedures will be completed remotely. We will purposefully recruit smokers who are not planning to quit in the next 30 days, and will examine baseline quit motivation (i.e., motivation to quit in the next 6 months) as a potential moderator of treatment effect. Results will advance our understanding of the behavioral process of practice quitting and the mechanisms governing PQA-focused treatment strategies. This mechanistic evidence will address a key gap in the smoking cessation treatment development literature, with the potential to increase intervention reach and efficacy to reduce tobacco-related morbidity and mortality.