The urinary excretion of cyclic adenosine 3',5'-monophosphate (cAMP), corrected for urinary creatinine, was determined in 177 patients with primary or metastatic tumours and in 149 normal subjects. In 26 patients with malignancy and in 10 control subjects the excretion of cyclic guanosine 3',5'-monophosphate (cGMP) was also evaluated. The urinary cAMP/Cr ratio in human neoplasms of epithelial origin was often significantly lower than normal, irrespective of the extension of malignancy. Surgical resection of the tumour, radiotherapy, or theophylline treatment increased urinary excretion of the nucleotide. In patients with malignancy, intravenous infusion of glucagon failed to produce the degree of elevation of plasma cAMP seen in normal subjects. Urines from patients with malignant neoplasms had low values of cAMP/Cr ratio with increased values of cGMP/Cr ratio. These findings could be the result of systemic alteration in synthesis or breakdown of the nucleotides.