Butyrylcholinesterase (BChE) is an enzyme that has been investigated for its putative role in neurodegenerative and neuropsychiatric disorders. The aim of our work was to study BChE activity variations in schizophrenic patients and to investigate the involvement of this enzyme in schizophrenia and the importance of determining its activity in this disease. This cross-sectional study was carried out 131 (104 males and 27 females, mean age = 38.0 ± 11.4 years) patients with chronic schizophrenia according DSM-IV criteria and 90 (64 males and 26 females, mean age = 37.1 ± 15.9 years) healthy controls. Plasma BChE activity was determined by a kinetic method on Integra 400plus(TM) (Roche Diagnostics). Patients with schizophrenia had higher plasma BChE activity than controls (P < 0.0001). Female patients had higher BChE activity and smokers had lower BChE activity than non-smokers either in patients and controls. In patients with schizophrenia, BChE activity was not differed with age, alcohol status and clinical sub-types, and was not correlated to duration of illness. Concerning therapeutic features, BChE activity was higher in patients treated with antipsychotics monotherapy than those treated with an association of antipsychotic and anticholinergic drugs, without significant difference (P = 0.196). Schizophrenic patients showed an increase BChE activity, which could be related to the pathophysiology of schizophrenia.