Smokers exhibit decrements in inhibitory control (IC) during withdrawal. The objective of this study was to investigate the neural basis of these effects in critical substrates of IC--right inferior frontal cortex (rIFC) and presupplementary motor area (pre-SMA). Smokers were scanned following smoking as usual and after 24-h smoking abstinence. During scanning they completed a Go/No-Go task that required inhibiting responses to infrequent STOP trials. Event-related brain activation in response to successfully inhibited STOP trials was evaluated in two regions of interest: rIFC (10 mm sphere, x=40, y=30, z=26) and pre-SMA (10 mm sphere, x=2, y=18, z=40). Smoking abstinence robustly increased errors of commission on STOP trials (37.1 vs 24.8% in the satiated condition, p<0.001) while having no effects on GO trial accuracy or reaction time (RT). In rIFC, smoking abstinence was associated with a significantly increased event-related BOLD signal (p=0.026). Pre-SMA was unaffected by smoking condition. The results of this preliminary study suggest that successful IC during withdrawal is associated with increased processing demands on a cortical center associated with attention to inhibitory signals.