Prefrontal functions impairment in schizophrenia and bipolar disorder are are markers of vulnerability to the diseases. Our previous data showed association between Wisconsin Card Sorting Test (WCST) performance in schizophrenia with the polymorphism of dopaminergic genes)COMT, DRD 1) and with polymorphism of Brain-derived neurotrophic factor (BDNF) in bipolar disorders. The Src-family tyrosine kinase Fyn plays important role in the interaction between BDNF and glutamatergic receptor NMDA in prefrontal cortex. The possible association between the polymorphisms of BDNF and Fyn genes and performance on WCST and N-back tests in healthy subjects were assessed in 200 healthy persons, genotyped for the two polymorphism of BDNF gene (C/T, Val66Met) and three polymorphisms of the Fyn gene (-93 A/G, IVS10+37T/C, Ex12+894T/G). In the whole group, the T/T genotype of C-270T BDNF polymorphism was associated with higher percentage of conceptual responses on WCST. Male subjects with C/T genotype obtained better results on percentage of correct reactions in N-back test. No significant differences between any of Fyn gene polymorphisms and WCST performance were found. Better results on percentage of correct reactions in N-back test were obtained by subjects with G/G genotype of 93A/G polymorphism and with G/G genotype of FYN T/G polymorphism. Female subjects having T/T polymorphism of T/C polymorphism performed better as to percentage of correct reactions in N-back test. The results obtained may suggest a contribution of BDNF and glutamatergic system genes to working memory efficiency in healthy subjects and bipolar disorder, while in schizophrenia with dopaminergic system genes.