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CETYLSALICYLIC ACID ( ASA) has beenA used for the treatment of rheumatoid arthritis for many years. Until recently, however, no methods have been available for the direct measurement of ASA in body fluids. Therefore, most of the data on the metabolism and distribution of ASA have been obtained indirectly by measuring salicylic acid, the metabolic product of the hydrolysis of ASA. A recent report indicated that when a relatively stable plasma salicylic acid level is maintained in patients with rheumatoid arthritis, the concentration of salicylic acid in the synovial fluid does not exceed that in the p1asma.l No similar data on ASA levels in the plasma and synovial fluid of such patients have been reported.In a recent study on the kinetics of ASA disposition in marl: we employed a specific and sensitive gas-liquid chromatographic technic which permits the direct measurement of small quantities of ASA in the presence of high concentrations of salicylic acid? In the present study this method was used to assess the distribution of ASA in the plasma and synovial fluid of patients with rheumatoid arthritis. For this purpose the concentration and rate of disappearance of ASA was determined by in vitro and in vivo measurements. MATERIALS AND METHODSSubjects. The study group consisted of 7 patients with definite rheumatoid arthritis as defined by Ropes et a1.,4 all of whom had knee joint effusions requiring arthrocentesis. At the time of study the patients were fasting and had omitted all medications for the preceding 6 hours, except one patient (O.D.) who inadvertently took 10 grains of aspirin 2% hours previously.Assay Technics. The methods used for assaying plasma levels of ASA by gas-liquid chromatographf and salicylic acid by spectrophotofluorometry6 have been described in detail previously.For gas-liquid chromatography, the plasma sample is extracted with ether and a silanizing reagent is added. The peak height ratio of the trimethylsilyl derivative of ASA to an internal standard (dibutyl maleate) is measured on a gasliquid chromatograph. The concentration of ASA is determined by comparing the peak height ratio with that obtained for a known standard assayed the same day. The technic was modified slightly for synovial fluid. To obtain consistent results, it was necessary to add 5 times as much silanizing reagent. We were unable to determine the chemical reason for this requirement.Procedures. For in vitro determinations specimens of joint fluid were obtained by arthrocen-