Cigarette smoking and/or nicotine administration have been shown to transiently ameliorate several psychophysiological deficits in patients with schizophrenia such as indicators of deficient sensory gating and attention, but acute effects of smoking on positive and negative symptoms in schizophrenia have not been evaluated in experimental paradigms. The current study assessed whether smoking of cigarettes, after 6-12 h abstinence, transiently alters the expression of negative and/or positive symptoms in patients with schizophrenia who have a history of regular smoking. In a double-blind, placebo controlled study patients with schizophrenia participated in two sessions in which they smoked either cigarettes moderately high in nicotine content or denicotinized cigarettes. They were interviewed pre-and postsmoking to obtain ratings of PANSS and SANS scales, and had blood pressure and pulse serially recorded before and after smoking. Pulse rate and blood pressure were slightly higher after smoking in the high nicotine cigarette session. Negative symptom scores on both scales were significantly lower after cigarette smoking compared to same-day predrug baseline, but there were no differences in active versus denicotinized cigarette drug effects. These results suggest that acute smoking of cigarettes reduces negative symptoms in patients with schizophrenia in this experimental paradigm. Future work needs to identify the mechanism responsible for this behavioral effect.