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The kinetics of disposition of lidocaine after intravenous regional anesthesia of the arm and direct intravenous infusion were studied in volunteers. Plasma levels of the drug in blood samples from a contralateral artery and in some cases also from the pulmonary artery and a contralateral vein were determined by gas chromatography. Peak plasma levels of lidocaine after cuff release (iv regional anesthesia) were 20 to 80 per cent lower than those found when the same dose was given directly into a vein over three minutes. Peak levels after cuff release were inversely proportional to tourniquet-application time; they also tended to be lower (by about 40 per cent) when the same dose was given in 0.5 per cent instead of 1.0 per cent solution. During the first few minutes after cuff release, distribution of lidocaine within the pulmonary system buffers the vital organs against high blood levels of the drug. Computer analysis of the data afforded estimates of the amount of drug remaining in the arm as a function of time after cuff release. Release of drug into the systemic circulation was found to be biphasic, an initial fast release of about 30 per cent of the dose, followed by a gradual washout of the remainder. Calculations indicated that even 30 minutes after cuff release about 50 per cent of the dose still remained in the arm. If anesthesia is to be re-established following cuff release this may be possible 10 to 30 minutes after initial release by injection of about half of the original dose following reinflation of the cuff.