We previously reported an association of Dysbindin gene (DTNBP1) variants with Bipolar Disorder I (BPI) patients (Pae, C. U., A. Serretti, et al. (2006)). This paper extends previous results investigating the possible role of DTNBP1 variants on response to acute mood stabilizer treatment. Moreover, we recently reported positive association results of heat-shock -70 family proteins (HSP70) and genetic variations and antidepressant response (Pae, C. U., A. Serretti, et al. (2007)). Since evidence stands for a possible involvement of chaperone activity in Bipolar Disorder pathophysiology, a pharmacogenetic approach was used to investigate the role of HSP70 on acute antimanic effect. A sample of 45 BPI were treated for an average of 36.52 (±19.87) days with mood stabilizers (lithium, valproate, carbamazepine), evaluated using the Clinical Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C) and HSP70 variants (rs2227956 C/T, rs2075799 A/G, rs1043618 C/G, rs562047 C/G, rs539689 C/G). No association was found between the investigated variations and response to mood stabilizer treatment even considering possible stratification factors. The small number of subjects is an important limitation to our study, nonetheless, Dysbindin and HSP 70 seem not to be involved in acute antimanic efficacy.