The coexistence of bipolar disorder (BD) and multiple sclerosis (MS) is well known. Manic symptoms may represent initial symptoms of MS, at least in some cases, and follow the MS-HLA phenotype frequencies. The purpose of this study was to examine the possible relation of BD and MS based on an HLA family study of a woman with BD and comorbid MS, with family history of BD. Five members of the family from three generations (the patient, her mother, her brother, and her two daughters) were examined regarding the two disorders and the HLA class I and II specificities, performed by serology and molecular techniques. Her deceased father, her brother, and her older daughter suffered from BD. Moreover, in her brother, BD and MS comorbidity was diagnosed. The three affected members and the nonaffected grandmother share the same class I and II, HLA-A2, B18, CW8, DR2, DQ1 haplotype. The shared class II, HLA-DR2, DQ1 haplotype among affected individuals, which is well known to be associated with MS in Caucasians, suggests a possible susceptibility locus for BD, mapped on chromosome 6, very close to the HLA region, underlying the clinical comorbidity of the two disorders.