We have measured plasma calcitonin (CT) in 135 untreated eucalcemic men with lung cancer and a control/ smoker population. CT levels were determined by RIA and validated by immunoextraction. Plasma immunoreactive CT moieties were purified by immunoadsorbent chromatography, treated with mercaptoethanol and urea, and characterized by gel filtration. Artifacts in human CT RIAs of cancer patient plasmas were detected by parallel plasma incubations in a salmon CT RIA system, which does not detect human CT, and by imrau-noprecipitation of tracer at the end of RIA incubations. Heating fresh plasmas to 65 C for 1.5 h reduced RIA artifacts without loss of CT moieties. Such characterization of hypercalcitonine-mia in each of the histopathological types of lung cancer has raised some important questions about the interpretation of plasma CT RIA measurements in lung cancer. Based on inhibition of tracer-antibody binding, plasma CT seemed to be elevated in 18‥ (14 of 80 samples) of the basal plasma samples obtained fr...