The pharmacokinetics of ropivacaine were evaluated during long-term continuous epidural analgesia (CEDA) for about 120 h. The total and free plasma concentrations of ropivacaine and the alpha1-acid glycoprotein (AAG) concentration were measured in 12 patients after total knee arthroplasty. The infusion rate was adjusted according to patients' analgesic needs or side effects. The mean (SD) rate of infusion of ropivacaine (Naropin 2 mg ml(-1)) was 14.6 (3.2) mg h(-1) on the day of surgery and was increased after surgery to 15.4 (4.4) mg h(-1) on days 1-5. This was equivalent to an absolute dose of 1786 (553) mg of ropivacaine over the entire infusion period. After an initial increase, the mean free ropivacaine plasma concentration nearly plateaued and than decreased slightly after approximately 70 h. The individual peak free plasma concentration was 0.096 (0.034) microg ml(-1). The highest individual free plasma concentration was 0.16 microg ml(-1). The individual peak total plasma concentration, 4.1 (1.2) microg ml(-1), was achieved after 67.7 (16.5) h, although the AAG concentration increased throughout the observation period. Our data support the safety and efficacy of long-term ropivacaine CEDA.