Cortisone and hydrocortisone labeled with C14 were found to disappear from the synovial cavity rapidly and at the same rate when injected intra-articulk Iy. Only a small portion of injected steroid was metabolized locally. Transformation of cortisone to hydrocortisone by synovial tissue was not observed. Esseva constatate que cortisona e hydro-cortisona, marcate con C14, dispare rapidemente ab le cavitate synovial. 1110s dispare con le mesme rapiditate como post lor injection intra-articular. Sol-mente un micre portion del injicite steroides esseva metabolisate localmente. Le transformation de cortisona in hydro-cortisona per histos synovial non esseva observate. HE INTRA-ARTICULAR injection of hydrocortisone and hydrocorti-T sone acetate is followed by a decrease or disappearance of pain and swelling of the affected joint and reduction in intra-articular temperature in most patients with rheumatoid arthriti~.l-~ Conversely, cortisone acetate and cortisone administered intra-articularly are ineffective as local anti-inflammatory agents. Differences in solubility probably do not account for this disparity, since both the acetate derivatives of hydrocortisone and corti-sone are less soluble in aqueous fluids than either of the parent steroid^.^ Nor do differences in the rate of disappearance (diffusion) plus metabolism of the two steroids from the synovial cavity explain the divergence in anti-inflammatory activity, since studies have revealed no significant difference in this parameter.5 Cortisone and its acetate, when administered systemically, are effective anti-inflammatory agents, being approximately two-thirds as active as hydro-cortisone on a weight However, when so administered, cortisone and its acetate are both very rapidly transformed to hydrocortisone, presumably in the liver.a The possibility exists that cortisone is biologicaIly inactive until transformed to hydrocortisone, and that the synovium is unable to effect such a transformation. In an earlier study using chromatographic methods, hydrocortisone was found in the synovial fluid of one of two patients following the intra-articular injection of c o r t i s ~ n e. ~ J ~ The present study was under-taken to reexamine this question with the use of isotopic technics. METHODS Two patients with active rheumatoid arthritis and moderate effusions in the knees were used for these studies. In one subject (G. M. I, fig. l) , 0.1 mg. cortisone-4-Cl4 (specific activity 2,800 counts per minute per /Ag.) dissolved in 5 ml. of 5 per cent ethanol in sterile normal saline was injected into one knee, which was then flexed and massaged repeatedly to effect mixing of the steroid with the synovial fluid. Samples of synovial fluid (1 to 3
