Calcitonin precursor (CTpr) levels are both markers and mediators of inflammation. The duration of their elevation after intravenous endotoxin challenge and the effects of anti-inflammatory therapies were studied in 52 subjects. CTpr levels maximized at 24 h in all subjects. At 7 days (n=4), after levels of acute-phase cytokines and C-reactive protein had normalized, CTpr levels remained 2-4-fold above baseline levels. The elimination half-life of CTpr levels ranged from 26.9 to 45.7 h. At 24 h, endotoxin and ibuprofen (compared with endotoxin alone) increased CTpr levels approximately 2-fold (P=.03), whereas soluble tumor necrosis factor receptor blunted the increase in CTpr levels by 2-3-fold (P=.0015). However, soluble interleukin-1 receptor failed to alter the increase in CTpr levels. Thus, the fact that anti-inflammatory agents may alter CTpr levels resulting from a single stimulus must be considered when CTpr is used as a clinical marker. Of importance, this study reveals that anti-inflammatory agents may modulate the CTpr level, which is a potential toxic mediator of inflammation.