α1‐Acid glycoprotein (AAG) concentrations were measured every 2 to 3 days in eight trauma patients and seven healthy subjects for approximately 3 wk. Mean AAG concentrations in the trauma patients rose from 100 mg/dl to a peak value of 243 mg/dl at 10 to 14 days. AAG levels averaged more than 200 mg/dl at 15 to 21 days. Mean AAG concentration in healthy subjects was 70 mg/dl with little inter‐ or intraindividual variability. Lidocaine was added to all serum samples from four of the patients and to selected samples from all of the healthy subjects and protein binding was determined. The binding ratio (bound concentration/free concentration) correlated strongly with AAG concentration in the trauma patients (r = 0.92), in the healthy subjects (r = 0.84), and in both groups combined (r = 0.96). AAG concentration and binding ratio for each of the four patients individually also correlated (P<0.05 in all cases). The change in free fraction associated with this increase in AAG was approximately doubled in each patient. Similar findings with drugs commonly used in trauma patients would be expected to alter serum concentration‐response relationships significantly.Clinical Pharmacology and Therapeutics(1982)31, 62–67; doi:10.1038/clp