An 18-year-old boy with clinical features of Klinefelter's syndrome in whose case the buccal smear was chromatin-negative and chromosomal analysis of peripheral blood revealed 46 XY karyotype is described. Diagnosis was confirmed by demonstration of an XXY cell line in cultured skin fibroblasts. Low circulating thyroxine levels were found despite absence of clinical hypothyroidism, and TSH was barely detectable. The studies are consistent with an isolated deficiency of thyrotropin-releasing hormone in a patient with XY/XXY mosaicism.