Plasma levels and 24-h urinary excretion of cyclic AMP and cyclic GMP were measured in 18 patients with hyperthyroidism, 7 patients with hypothyroidism and 25 normal subjects. Mean plasma and urinary levels of both cyclic AMP and cyclic GMP were significantly positive correlations between the serum thyroid hormone levels and plasma and urinary cyclic nucleotide concentrations were also found, suggesting that the elevated extracellular cyclic nucleotide levels in hyperthyroidism are probably a consequence of increased secretion of thyroid hormones. In the hypothyroid patients the extracellular cyclic nucleotide concentrations did not differ significantly from those of the normal subjects.