Two independent lines of evidence support the localization of a schizophrenia susceptibility locus to the proximal long arm of chromosome 5. A partial trisomy of chromosome 5 (5q11.2-q13.3) cosegregates with the disorder in a Canadian family of Chinese descent, and DNA markers from proximal 5q cosegregate with schizophrenia (plus related disorders) in families of British and Icelandic descent. We constructed a human:hamster hybrid cell line (HHW 1064) whose only human complement is a chromosome 5 that is missing the trisomic region associated with schizophrenia. In combination with a "matched" cell hybrid (HHW 105) containing an intact chromosome 5, we physically mapped DNA markers relative to the trisomy. "Schizophrenialinked" DNA markers p105-153Ra (D5S39) and p105-599Ha (D5S76) map within the trisomy and proximal to the 5q11.2 breakpoint, respectively. The hybrid cell lines HHW 105 and HHW 1064 together provide a means to identify and generate syntenic DNA markers to further investigate the location of a schizophrenia locus.A report by Bassett et al. (1988) describes the coin-heritance of a chromosomal triplication, 5q11.2-5q13.3, with schizophrenia in a well-characterized Canadian family of Chinese descent. The two affected members of this family, a 20-year-old man and his 53-year-old uncle, share a phenotype of neuroleptic responsive schizophrenia with typical psychotic and deficit symptoms. The affected individuals also suffer mild physical anomalies which prompted clinicians to investigate and subsequently discover a chromosomal abnormality associated with the occurrence of schizophrenia in this family. High-resolution karyotyping revealed a balanced direct insertion (46, XX, inv ins) (1;5) (q32.3; q13.3-q11.2) in an unaffected relative (the mother and sister, respectively) of the two affected probands. Both affected individuals were trisomic for the translocated 5q segment, whereas other unaffected relatives had normal genomic karyotypes. This finding encouraged several laboratories to test DNA markers from the long arm of chromosome 5 for linkage to the disease phenotype in large schizophrenia pedigrees. Recently, one group has reported linkage with markers from the proximal portion of 5q to seven British and Icelandic families (Sherrington et al., 1988), while several groups report the absence of linkage in other kindreds (Kennedy et al.,