The circadian and pulsatile TSH secretion profiles were investigated in 5 females at the time of menstruation and 21 healthy males by sampling blood every 10 min for 24 h. Computer-assisted analysis, i.e. the Cluster and Desade programs, revealed means of 9.9 +/- 1.7 (Cluster) and 11.4 +/- 3.9 (Desade) pulses/24 h. More than 50% of the TSH pulses were detected between 2000-0400 h. Male and female subjects showed no significant difference in the basal mean and pulsatile secretion of TSH or in the TSH response to TRH (200 micrograms). Repetition of the TSH secretion analysis in 4 healthy subjects after 1, 2, and 6 months (2 subjects) revealed a significantly better cross-correlation within than between individuals (P less than 0.0001). We modulate the circadian TSH secretion pattern by acute sleep withdrawal or prolonged sleep after a night of sleep withdrawal in six healthy male volunteers. Sleep withdrawal augmented the nightly TSH secretion (mean serum TSH, 2.1 +/- 1.3 mU/L; mean TSH in sleep, 1.3 +/- 0.5 mU/L; P less than 0.05), whereas sleep after sleep withdrawal almost completely suppressed the circadian variation (mean TSH, 1.1 +/- 0.7 mU/L; P less than 0.01). This modulation is due to a significant decrease in pulse amplitude, but not to an alteration in the frequency or temporal distribution of TSH pulses.