Recently, it was shown that schizophrenia is accompanied by an activation of the inflammatory response system with signs of an acute phase response, such as increased plasma haptoglobin (Hp) concentrations. Hp is characterized by a molecular variation with three known phenotypes, i.e. Hp 1-1, Hp 2-1 and Hp 2-2. The aim of the present study was to examine Hp phenotypic and genotypic frequencies in schizophrenic patients. Hp phenotyping was carried out in 98 Northwestern Italian schizophrenic patients and the phenotypic and genotypic distributions were compared with the distributions established in the Northwestern Italian population. Plasma Hp concentrations were determined by means of a laser nephelometric method. The allele frequency of the Hp phenotypes in schizophrenia, i.e. Hp 1-1 (9.2%), Hp 2-1 (38.8%) and Hp 2-2 (52.0%), was significantly different from that in the Northwestern Italian population, i.e. Hp 1-1 (17.0%), Hp 2-1 (51.3%) and Hp 2-2 (38.5%). The frequency of the Hp-2 gene was significantly higher in schizophrenic patients (71.7%) as compared with the observed frequency in the Northwestern Italian population (62.5%). The alterations in Hp phenotypic and genotypic distribution were more pronounced in the schizo-affective, disorganized, undifferentiated and residual schizophrenic patients than in paranoid schizophrenic patients. More than a third (35.7%) of the schizophrenic patients showed plasma Hp concentrations which were higher than the upper limits of normality. Schizophrenia is accompanied by an altered distribution of the Hp phenotypes and genotypes, suggesting that genetic variation on chromosome 16 may be associated with schizophrenia.