Bupivacaine pharmacokinetics were determined in 11 patients receiving the drug intra-articularly after knee arthroscopy performed under general anesthesia. Forty ml 0.25% bupivacaine was given at the end of surgery and the thigh tourniquet was released 2 to 3 minutes after injection. Blood samples were obtained up to 5 hours after tourniquet release and plasma bupivacaine concentrations were determined. Pharmacokinetic parameters determined were (mean +/- SD): volume of distribution (Vd beta) 206 +/- 88 L, clearance (Cl) 0.816 +/- 0.378 L/min, terminal half-life (T1/2) beta 189 +/- 84 minutes, absorption rate constant (ka) 9.92 +/- 6.79/min, estimated peak plasma concentrations (Cpmax) 0.48 +/- 0.20 micrograms/mL, and time to peak concentration (tmax) 43.4 +/- 23.1 minutes. Results indicate that injections of 100 mg bupivacaine intra-articularly after knee arthroscopy produce peak blood concentrations within the first hour after surgery, and that these will be well below concentrations associated with toxic reactions. Peak concentrations can be minimized with shorter tourniquet inflation times and with longer intervals between injection and tourniquet release.