OBJECTIVE: Animal models suggest that N-acetylcysteine inhibits cocaine-seeking. The present pilot study evaluated whether N-acetylcysteine would suppress reactivity to cocaine-related cues in cocaine-dependent humans. METHOD: In this double-blind, placebo-controlled trial, 15 participants received N-acetylcysteine or placebo during a 3-day hospitalization. Participants were crossed over to receive the opposite condition on a second, identical 3-day stay occurring 4 days later. During each hospital stay, participants completed a cue-reactivity procedure that involved collecting psychophysical and subjective data in response to slides depicting cocaine and cocaine use. RESULTS: While taking N-acetylcysteine, participants reported less desire to use and less interest in response to cocaine slides and watched cocaine slides for less time. CONCLUSIONS: The inhibition of cocaine cue reactivity is consistent with existing preclinical data and supports the use of N-acetylcysteine as a treatment for cocaine dependence.