Previous studies have demonstrated possible linkage between chromosome 22 and one of the hypothesized schizophrenia susceptibility genes. Interpretation of these data, however, is not straightforward: although not significant at the level traditionally accepted to demonstrate linkage, reported lod scores were greater than should have occurred by chance for an unlinked marker based on simulation studies. Further, these studies used sample populations which were either of mixed nationality and ethnicity, or mixed ethnic ancestry from one country. We therefore tested for linkage between highly polymorphic chromosome 22 markers and schizophrenia in a sample of southern African Bantu-speaking black families, a population known to have diverged within the last 2,000 years. We also tested one candidate locus, the gene for the soluble form of catechol-O-methyl transferase (COMT) located at 22q11, which has been suggested as the cause of psychiatric symptoms observed in velo-cardio-facial syndrome (VCFS, including DiGeorge syndrome), and which is known to be functionally as well as genetically polymorphic. There is no evidence to support the linkage of markers on chromosome 22 to susceptibility to schizophrenia in this population, using either parametric or nonparametric analysis.