Previously we reported evidence for genetic linkage between markers on chromosome 22q12 and schizophrenia in 23 multiply affected pedigrees. As part of further investigation of this region, we have applied the transmission disequilibrium test (TDT) to the genotype data. The TDT is a test for both linkage and linkage disequilibrium, and is based on the unequal probability of transmission of two different marker alleles from parents to affected offspring. We obtained significant results for the marker D22S283 (chi 2 = 35.9, 14 df, p = 0.001), D22S278 (chi 2 = 16.5, 6 df, p = 0.01) and F8VWFP (chi 2 = 13.1, 4 df, p = 0.01). Application of the Bonferonni correction for testing multiple markers renders the results for marker D22S278 and F8VWFP non-significant (from p = 0.01 to p = 0.14), while the result for D22S283 remains modestly significant at p < 0.02. Overall, our findings strengthen the suggestion that the region around D22S283 contains a susceptibility gene for schizophrenia.