The hypothesis that at least a subgroup of familial cases of schizophrenia could be due to a genetic defect on the X chromosome is supported by the observation of an excess of X-chromosome aneuploidies (XXX and XXY) among populations of patients with psychosis. The distal long arm, Xq27-q28, is a candidate region where linkage has been claimed to manic-depressive disorder and a fragile site has been associated with schizophrenia spectrum disorders. The present study excluded linkage to a large part of this region using four polymorphic probes and multipoint lod-score analysis in 10 families with multiple members with schizophrenia.