Although the radioimmunoassay of serum calcitonin (CT) has facilitated the diagnosis of medullary thyroid cancer (MTC) one may encounter patients whose basal serum levels of CT are normal or nearly normal. In such cases clinicians have utilized intravenous stimulation tests such as calcium or penta-gastrin to obtain a diagnostic increase in serum CT. We have reported finding immunorcactive CT in the urine of man and have found it to be a useful technique for the diagnosis and study of patients at risk for MTC or other hypercalcitonemic diseases. Using basal urine CT alone we were able to separate 73% of patients at risk for MTC into clearly normal or abnormal groups. For the remaining 27% a stimulation test with subsequent determination of urine CT was required. The radioimmunoassay of urine CT is a simple, reliable, accurate test for the screening diagnosis of MTC. A protocol for the screening workup of a patient at risk for MTC is given.