Recent reports of a linkage trend in 6p24-22 for schizophrenia (SZ), in different samples, were tempered by the concurrent evidence of negative reports in other samples. In the studies showing positive results, different definitions of affection and a wide spectrum of diagnoses were used. Our objectives were not only to test for linkage at 6p24-22 in the Eastern Quebec population, but also to test whether this putative vulnerability locus was either selectively linked to schizophrenia (SZ), or to bipolar disorder (BP), or to both major psychoses. Parametric and nonparametric linkage analyses with 12 microsatellite markers in 6p24-p22 were performed on a sample of 18 large multigenerational pedigrees (N = 354) either affected by SZ, or by BP, or equally affected by both major psychoses (i.e., mixed pedigrees). Three affection definitions were usually tested in our program: one on schizophrenia (SZ), one on bipolar disorder (BP), and one that comprised SZ and BP under the hypothesis of a susceptibility locus common to both in major psychoses (common locus, CL). The results of parametric analyses did not support a major gene hypothesis. However, in one large mixed pedigree (#151), we observed with the common locus phenotype (CL) lod scores of 2.49 and 2.15, respectively, at the D6S296 and D6S277 loci under a dominant model. Our data suggest the presence of a potential vulnerability locus at 6p24-22 that could be related to both schizophrenia and bipolar affective disorder. These results may be seen as congruent with former studies that used schizoaffective as well as schizophrenia diagnoses as entry criteria for the affected families, and used an affection definition that comprised affective psychoses as well as schizophrenia.