There is evidence to suggest that dysfunction of dopaminergic neurotransmission in the central nervous system (CNS) plays a role in the etiopathology of schizophrenia. Epidermal growth factor (EGF) gene polymorphism has an impact on EGF production in mononuclear cells, and EGF seems to affect the development of midbrain dopaminergic neurons. The few studies concerning EGF gene polymorphism and schizophrenia have yielded contradictory results. Our aim was to investigate whether EGF gene A61G polymorphism predisposes to schizophrenia, and this polymorphism was therefore studied in 149 schizophrenic patients and in 94 healthy controls using 5' nucleotidase assay (TaqMan). As far as EGF A61G polymorphism was concerned, we detected no significant differences in the allele and genotype frequencies between the patients and the controls. However, the G/G genotype was significantly associated with an earlier age of onset of schizophrenic psychosis in male subjects (P=0.005) as well as in the entire population, but not in female patients (P=0.008 and 0.46, respectively). The average age (+/-SD) of onset of schizophrenia was 20.1+/-3.9 years in male EGF A61G G/G homozygotes and 23.7+/-6.6 (P=0.02) years in other genotypes. In conclusion, EGF gene polymorphism was not associated with the risk of schizophrenia. However, the EGF G/G genotype, which has been suggested to involve abundant production of EGF, was associated with early onset of schizophrenia in male patients.