The high prevalence of smoking among individuals diagnosed with schizophrenia is well recognized and documented. Many explanations have been put forth to explain this phenomenon including the effects of antipsychotic medication. We sought to determine if there is a difference in smoking behaviour between patients treated with clozapine and depot neuroleptics. This cross-sectional study recruited patients with schizophrenia from the Forensic Psychiatric Institute of British Columbia. Eligibility for the study required that patients be on either clozapine or depot neuroleptic for at least 2 months. The patient's smoking behaviour was evaluated using expired carbon monoxide (CO) measurements, the Fagerstrom Test for Nicotine Dependence (FTND), and a semi-structured interview. Our results showed that patients treated with clozapine had significantly lower expired CO values than patients treated with depot neuroleptics (11.8 +/- 9.2 versus 21.2 +/- 7.1 p.p.m., respectively, P < 0.01). This finding was further supported by the noted trend in which patients receiving clozapine self-reported smoking less than patients treated with depot neuroleptics (13.7 +/- 11.3 versus 26.8 +/- 18.3 cigarettes per day, respectively, P = 0.08). Thus, according to measurements of expired CO levels, patients treated with clozapine smoke less than patients treated with depot neuroleptics.