OBJECTIVE Genetic factors are known to be important in the etiology of bipolar disorder (BD). The fragile sites (FSs) are a very interesting subject for the study of clinical disorders. The aim of this study was to evaluate fragile sites seen in patients with bipolar disorder and find a correlation between some fragile sites and bipolar disorder. METHODS The frequencies of folate sensitive FSs were compared in short-term whole blood cultures from bipolar patients and from normal individuals. RESULTS The rate of FS expression in the patients was considerably higher than in the controls (p < 0.001). Several chromosome regions including 1p36, 1q21, 1q32, 3p25, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22 and Xq26 were represented considerably more often in the patients than in the controls (p value between 0.001 to 0.036). Among these FSs, the sites 1p36, 1q21, 3p25, 7q22, 7q32, and 14q24 were not observed in other studies. CONCLUSIONS These regions can be the most active of hot spots in the genomes of bipolar patients, and may harbor important genes associated with BD.