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We have tested the hypothesis that alpha-adrenergic drive is involved in the nocturnal increase in TSH in man. Seven mildly hypothyroid women (basal TSH levels 5.0-11.0 mU/l), aged 38-60 years, and nine euthyroid women, aged 27-60 years, were studied. Subjects underwent alpha-adrenergic blockade by infusion of thymoxamine (210 micrograms/min from 19.00 to 24.00 h); the same women were used as controls, with saline infused on different nights. Subjects were not allowed to sleep during the study period. A clear evening rise in basal TSH levels was apparent in both normal subjects and patients. Although overall secretion of TSH was slightly decreased in normal subjects (mean +/- S.E.M. area under the curve, 29.93 +/- 0.96 vs 30.71 +/- 0.80 mU/l per h; P less than 0.05), thymoxamine infusion did not produce any major alteration in the gradual rise in TSH levels during the evening (incremental change above baseline +0.96 +/- 0.21 during control infusion and +0.97 +/- 0.27 mU/l during thymoxamine infusion). In mildly hypothyroid patients the TSH changes were exaggerated and alpha-adrenergic blockade caused a reduction in basal TSH levels and a delayed rise in TSH (incremental change above baseline +2.93 +/- 1.42 during control infusion and +2.26 +/- 0.73 mU/l during thymoxamine infusion; P less than 0.02). Overall TSH secretion was significantly decreased by thymoxamine (mean +/- S.E.M. area 106 +/- 2.45 mU/l per h vs 123.32 +/- 3.68 in the control study; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)