The aim of this study was to explore the occurrence of abnormalities in the circannual thyrotropin (TSH) rhythm in Klinefelter’s syndrome (KS). For 3 years, 69 healthy adult males and 73 patients with KS, usually living in Sardinia, were studied by a cross-sectional design. Plasma samples were taken between 08.00 and 09.00 h and TSH was radioimmunoassayed. First, the mean (± SD) of the data, grouped for each month of the year, was estimated to seek any macroscopic annual variation. Then, a cosine function was fitted to the single serially independent data by the single cosinor method in order to test for any statistically significant rhythm and, if the no-rhythm assumption is rejected, to describe the circannual parameters. Our patients showed circannual mean TSH concentrations lower than controls (p < 0.001) without any statistically significant circannual rhythm, which was instead apparent in normal subjects with the annual crest time in December (95% CL November–February). Our results support the hypothesis that in KS the impaired TSH secretion may be related to abnormalities in the hypothalamic-pituitary coordination of the circannual rhythmicity of this hor