Five hundred and seventy nine Chinese patients with schizophrenia who met DSMIV criteria for the disorder were genotyped for alleles epsilon 2,3,4 of apolipoprotein E (APOE) gene. All were recruited from inpatients and outpatients attending a large mental health centre in Shanghai. Results were compared to APOE data on 1528 controls drawn from the same area. Major differences in APOE genotype ratios and allele frequencies were observed between the patients and controls. The patients with schizophrenia had highly significantly (p<0.0001) increased epsilon 4/-genotypes and allele frequencies, and decreased epsilon 3/3 genotypes and epsilon 3 allele frequencies compared to controls. The effect was independent of sex and/or age of onset of illness, but strongly influenced by date of birth. Significant differences were restricted to individuals with schizophrenia born either before 1949 or during the period 1958-1967. Both were times of severe food shortages and malnutrition. We suggest that APOE may operate as an additional risk factor for schizophrenia in individuals subjected to fetal and/or early postnatal malnutrition.