Nicotine has been proposed to provide anxiety relief, oral gratification and self-medication of psychotic symptoms in psychiatric patients. In order to investigate the relations between psychopathology and tobacco use we measured the concentration of cotinine, the major metabolite of nicotine, in the saliva of psychiatric patients and healthy volunteers. In a sample of 42 schizophrenic patients we correlated smoking status, cotinine levels, symptom profiles (PANSS), and neuroleptic side effects (Simpson–Angus). Despite reporting the same amount of cigarettes consumed per day the saliva concentration of cotinine was significantly higher in patients with schizophrenia than in the controls. There were no significant differences in clinical characteristics between smoking and non-smoking schizophrenic patients, but smokers tended to be on higher drug doses. High cotinine concentrations correlated significantly with the negative symptoms Passive withdrawal and Social avoidance. The results indicate that the schizophrenic patients smoke cigarettes more intensely than other patients and healthy subjects. The correlation between high cotinine levels and negative symptomatology may reflect an attempt by schizophrenic patients to overcome the emotional withdrawal and thus the results may lend support to a self-medication hypothesis.