The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intra-familial marriage among its members. High infection rate (23%) by Human T-Lymphotrophic Virus type-I (HTLV-I) was found in this population. The known modes of HTLV-I transmission are by sexual intercourse, from mother to child in breast milk, via blood transfusion, and by sharing of needles by parenteral drug users. In the present study we examined the presence of HTLV-I infection in high-risk psychiatric patients of Iranian origin in order to evaluate the infection rate in socially isolated subjects. We screened and examined all (N=42) Iranian-born schizophrenic patients in our center, of whom 17 were Mashhadi subjects (7 females, 10 males, mean age 48.7±13.2 years), and 25 were born in Iran in other cities than Mashhad (12 females, 13 males, mean age 43.2±11.9). Blood samples were tested for HTLV-I antibodies by particle agglutination test. The polymerase chain reaction (PCR) was used to detect HTLV-I proviral DNA sequences from peripheral blood mononuclear cells. One Mashhadi-born Jew (5.9%) was seropositive and PCR-positive for HTLV-I. None of the schizophrenic non-Mashhadi Iranian subjects was positive for HTLV-I by either method. This infection rate in schizophrenic patients of Mashhadi origin is significantly lower than rates reported for the normal Mashhadi community. We suggest that the relative isolation imposed by the stigma associated with mental illness and recurrent psychiatric hospitalizations serve to protect this sub-group from HTLV-I infection.