BACKGROUND: Parathyroid hormone-related protein(PTHrp) was first identified as the cause of hypercalcemia in malignancy. Hypercalcemia can be found in malignancy, especially in the epidermoid carcinoma of the lung, even without extensive metastases to the bones. The application of sensitive assays for PTHrp may help in the early diagnosis of lung cancer, in the monitoring of treatment and in the detection of recurrence. METHOD: Serum PTHrp was measured by radioimmunoassay detecting the N-terminal 1~34 peptide of human PTHrp(PTHrp 1-34) in 63 histologically confirmed lung cancer patients and 22 healthy controls. RESULT: Serum PTHrp(mean+/-S.E.) was 312+/-68.9pg/ml in 63 lung cancer patients and 158+/-38.2 pg/ml in 22 controls(p>0.05). PTHrp was 356+/-103.9pg/ml in 34 epidermoid carcinoma patients, 281 +/-148.7pg/ml in 15 adenocarcinoma patients and 316+/-140.8pg/ml in 9 small cell carcinoma patients. In epidermoid carcinoma patients, PTHrp was 570+/-472.3pg/ml in stage II(n=3; p<0.05 vs controls), 166+/-22.4pg/ml in stage IIIa(n=9), 282+/-113.3pg/ml in stage IIIb(n= 12) and 668+/- 367.9pg/ml in stage IV(n=9; p<0.05 vs controls). PTHrp was significantly increased in 8 epidermoid carcinoma patients with bone metastases(1526+/-811.2 pg/ml; p<0.0005 vs controls). Hypercalcemia was observed in an epidermoid carcinoma patient whose PTHrp value was 244 pg/ml. CONCLUSION: The serum PTHrp was increased in advanced epidermoid carcinoma patients even without hypercalcemia. The measurement of PTHrp may be not helpful in the early diagnosis of lung cancer. But the lung cancer should be suspected in the marked elevation of PTHrp. It may be of value in detecting patients of advanced diseases witn bone metastases or patients who might develop the malignancy associated hypercalcemia.