Elevated serum levels of the prohormone of calcitonin (CT), procalcitonin (ProCT), have been documented in illnesses such as inhalational burn injury, in several sepsis syndromes, and in endotoxemia. In this study, we measured and characterized the circulating precursor forms of CT during the course of infectious pneumonitis. The initial (mean +/- SEM) serum total multiform CT level in 12 patients with acute infectious pneumonia was 1,019 +/- 430 pg/mL. In comparison, the mean level of total CT for 19 age-matched control patients without lung disease was 32 +/- 6 pg/mL (P < 0.001). The mean serum total CT level on initial examination was greater in the 6 patients with bacterial isolates, at 1,793 +/- 752 pg/mL, than in those with nonbacterial infectious pneumonia, at 242 +/- 109 pg/mL (P = 0.018). After admission to the hospital, patients' serum total CT progressively declined concomitantly with the clinical resolution of the pneumonia; at discharge, mean serum level was 121 +/- 34 pg/mL. On discharge, the patients who had persistent radiographic abnormalities had significantly higher levels than did those who had complete resolution. Both the mean serum calcium and phosphate were significantly lower at the initial time of study than at discharge (P < 0.002 and P < 0.0004, respectively). Gel filtration chromatography of sera obtained during the acute pneumonitis phase revealed increased levels of precursor forms of CT, including ProCT; these levels diminished with clinical resolution. In an additional three patients, the serum total CT increased very rapidly after aspiration (within 6 to 12 hours); the peak levels were several times greater than the upper limits of normal. In these patients, the principal serum CT components were ProCT and other precursor forms. These results show that both infectious and aspiration pneumonitis are associated with a rapid increase in circulating ProCT and other precursor forms of CT.