To investigate the role of the apolipoprotein E (APOE) gene in schizophrenia, the authors analyzed 60 families with this mental disorder. An association in the presence of linkage test (APL) and haplotypes analysis were undertaken using the APL v1.1 software. A global allelic transmitted was significant for APOE-epsilon3 (chi(2)=6.24, p=0.01); this allele is mainly carried by female patients (chi(2)=8.33, p=0.003), whereas APOE-219G is preferentially transmitted in males (p=0.02). Furthermore, our results show that haplotypes APOE-epsilon3/APOE-219G are associated with schizophrenia (chi(2)=11.61, p=0.01). These results provide evidence that the APOE gene may play a significant role in the etiology of schizophrenia in the Mexican population.