The objective of this study was to examine whether the functional genetic polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene influences cognitive deterioration in a sample of patients with psychosis under treatment with atypical antipsychotics. Eighty-seven patients with psychosis were genotyped for this polymorphism and were assessed with three Wechsler Adult Intelligence Scale (WAIS)-III subtests (Vocabulary, Information, and Digit Symbol-Coding). Performance on these three subtests was used to compute a 'cognitive deterioration index', and the effect of COMT genotype on this cognitive deterioration index was examined. A linear relationship between the number of Val alleles and the score on the cognitive deterioration index (i.e. the more Val alleles, the more cognitive deterioration) was observed. These results confirm the role of COMT genotype in the cognition of patients under treatment for psychosis, suggesting that it influences the extent of their cognitive deterioration.