In man, the total amount of cyclic AMP (cAMP) excreted in urine is derived from (a) the filtered load of the nucleotide and (b) cAMP formed de novo in the kidney (nephrogenous cAMP, NcAMP). NcAMP is the only pool of the nucleotide easily quantified in vivo and appears to provide a specific index of the effects of circulating, active parathyroid hormone. Elevated values for NcAMP (4.64 ± 1.95 nmol/100 ml GF, mean ± SD) were found in 90% or more of 115 patients with primary hyperparathyroidism, and low values (0.31 ± 0.16 nmol/l00 ml GF, mean ± SD) were noted in 41 individuals with absent or suppressed parathyroid function. When properly expressed (as a function of glomerular filtration rate), results for the total cAMP excretion provided similar findings. The measurement of NcAMP provides a sensitive index of parathyroid function over the entire range of parathyroid activity and has proven to be an optimal method for assessing parathyroid suppressibility in response to intravenous or oral calcium administration. These techniques, the ‘calcium injection test’ and the ‘oral calcium tolerance test’, are useful in evaluation a number of subtle disorders of calcium metabolism.