Several cytogenetic surveys and literature reviews have suggested a possible association between Klinefelter's syndrome and bipolar illness. We describe a manic patient with Klinefelter's syndrome who was treated successfully with lithium. Our patient represents the 32nd reported case of bipolar disorder in an individual with a known chromosomal abnormality, the 15th with Klinefelter's syndrome, and the 11th with a karyotype of 47XXY.