RATIONALE: Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain structure including reduced gray matter (GM) volume and/or density in areas including frontal and cingulate cortices, thalamus, and insula. However, associations between brain structure and smoking cessation treatment outcomes have not been reported. OBJECTIVES: In the present analysis we sought to identify associations between regional GM volume--as measured by voxel-based morphometry (VBM)--and a smoking cessation treatment outcome (point prevalence abstinence at 4 weeks). METHODS: Adult smokers underwent high-resolution anatomical MRI scanning prior to an open label smoking cessation treatment trial. VBM was conducted in SPM5 using the DARTEL algorithm and relapser vs. quitter groups were compared using independent sample t tests (p < 0.001, uncorrected). Analyses controlled for potentially confounding factors including years smoked, cigarettes per day, total intracranial volume (TIV), and sex. RESULTS: Of 18 smokers, 8 achieved a 4-week point prevalence abstinence, confirmed by CO level (