Bupivacaine (Marcaine) pharmacokinetics were determined in 11 patients receiving the drug intraarticularly after arthroscopic procedures performed on the knee with patients under general anesthesia. Forty milliliters of 0.25% bupivacaine (100 mg) were given as a bolus into the intraarticular space of the knee of each patient. The thigh tourniquet was released 2-3 min after injection and blood samples were obtained 5, 10, 15, 20, 30, 60, 120, 180, 250, and 300 min after tourniquet release. Pharmacokinetic parameters obtained were (mean +/- SD): Vd beta 206 +/- 88 L; Cle 0.816 +/- 0.378 L/min; t 1/2 beta 189 +/- 84 min; ka 9.92 +/- 6.79 x 10/min; Cpmax 0.48 +/- 0.20 micrograms/ml; and tmax 43.4 +/- 23.1 min. Correlations between higher peak plasma concentrations and longer tourniquet times (p = 0.02) and shorter intervals from injection to tourniquet deflation (p = 0.03) were found using multiple linear regression. Our results indicate that injections of 100 mg of bupivacaine intraarticularly after knee arthroscopy will produce peak blood levels within the 1st h after surgery and that these levels will be well below those noted to produce toxic reactions. Peak levels can be minimized with shorter tourniquet inflation times and with longer injection to tourniquet release intervals. Ninety healthy adult outpatient knee arthroscopy patients also were studied to evaluate the effectiveness of bupivacaine in relieving postoperative knee discomfort when injected immediately postoperatively. The subjects were randomized into four groups: (a) intraarticular injection of saline, (b) intraarticular injection of bupivacaine, (c) subcutaneous injection of bupivacaine at the portal sites, and (d) both intraarticular and subcutaneous injection of bupivacaine.(ABSTRACT TRUNCATED AT 250 WORDS)