CYP2D6 has been suggested to be functionally similar to the dopamine transporter. The present study was aimed at analysing the frequency of CYP2D6 alleles and genotype among schizophrenic patients compared to healthy volunteers. CYP2D6 *3, *4, *5, *6, *10 and duplicated alleles were analysed in 128 unselected schizophrenia inpatients (SP) and 142 unrelated white European Spanish healthy volunteers (HV). SP and HV with >2, 2, 1 or 0 CYP2D6 active genes were 4.7, 64.8, 28.1 and 2.3%, and 6.3, 52.1, 33.1 and 8.5%, respectively. The frequency of homozygous for CYP2D6 inactive alleles or poor metabolizers (PMs) was lower (P<0.05) in SP than in HV. Furthermore, the frequency of CYP2D6 inactive alleles was also lower in SP than in HV (16.8 vs 25.7; P<0.05), specifically the CYP2D6*6 allele was not found among patients. The present study shows a lower frequency of PMs in schizophrenic patients than in healthy volunteers supporting the hypothesis of a potential role of CYP2D6 in the vulnerability to schizophrenia.