We studied the changes in the urinary cAMP level in fifty-five predialysis patients (30 men and 25 women) with chronic renal failure (CRF). The excretion of cAMP in 20 patients with first-degree CRF (serum creatinine levels below 356.6 mmol/I) and 15 patients with second or third degree CRF (serum creatinine below 800 mmol/I) was compared with that of 20 age-matched controls using the original I-125 RIA (radioimmunoassay) kit of Incstar Corporation, USA. The urinary cAMP was within normal limits in first-degree CRF patients (mean +/- Sx = 2,617 +/- 268.2 nmol/l) whose serum calcium level was slightly decreased. When calculated per 100 ml of glomerular filtration rate, their urinary cAMP level was significantly elevated--101.17 +/- 0.39--as compared with that of the controls--2.5 +/- 0.2. The urinary cAMP excretion was significantly higher in second and third degree CRF patients--mean 3,755 +/- 435.2 nmol/l, p < 0.05. This increase correlated with hypocalcemia whereas the serum alkaline phosphatase levels remained normal. 20% of the patients with second or third degree CRF had normal urinary cAMP excretion. In our opinion, urinary cAMP levels can reliably be employed as a sensitive and specific indicator of the onset of mild secondary hyperparathyroidism in predialysis patients with CRF.