To explore the role of apolipoprotein E (ApoE) in schizophrenia, we investigated ApoE phenotypes in a group of patients with schizophrenia. Serum samples were obtained from 122 schizophrenic patients and 126 controls in Japan and were examined using isoelectric focusing/immunoblotting. This experiment showed a trend toward a decreased frequency of ApoE epsilon4 in schizophrenia and no link between ApoE epsilon4 and familial schizophrenia or early onset schizophrenia. On the other hand, a decreased frequency of ApoE epsilon2 in early onset schizophrenia was detected. These results suggest that ApoE epsilon2 protects against early onset schizophrenia, and that ApoE epsilon4 is not involved in the development of schizophrenia in Japanese.