LTHOUGH THE PROPERTIES of radioactive isotopes have been exploited in many branches of internal medicine, it is only recently that their applicability to rheumatology has been recognized. In general, radioisotopes have been used in rheumatology as investigative rather than therapeutic agents, and apart from a short section on local treatment, the bulk of this review reflects this emphasis. From the earliest studies it was apparent that differences between inflamed and normal joints could easily be detected, whether the radioisotope was given intravenously or intraarticularly. 1~2~18~1g~34~40~4g~54~58~60~63~*4~89~ g7~9g~102~103 In the first case the presence of inflamed synovium was reflected in a greater accumulation (increased uptake) of radioactivity in the diseased as opposed to the normal joint. When the isotope was injected into the joint cavity, its subsequent rate of disappearance from the inflamed joint was faster than from the normal joint. Since the mechanisms involved are so different, these methods of displaying inflammed joints will be considered separately in this review. However, certain generalities apply to both situations. First, both methods are nonspecific, both in terms of the nature of the inflammatory disease and in terms of the radioisotope used in the study. Thus, similar degrees of abnormality of radioisotope uptake or clearance rate may be found in rheumatoid arthritis, Reiter’s disease, septic arthritis, psoriatic arthritis, acute gouty arthritis, and systemic lupus erythematosus.28~34~43~4g~6*~71~90~g5~g7~103 Increased uptake may be demonstrated using radioactive technetium ( ggm Tc) or radioiodinated serum albumin, and increased clearance rates are obtained with radioisotopes as dissimilar as radioactive xenon (133Xe) and radioactive sodium (Z4Na).28~37~43~102~L06 A corollary to this is that these radioisotopic methods cannot be expected to provide information of a primarily diagnostic nature. Second, the abnormalities shown by both methods reflect the severity of clinical involvement in the disease process and may be used to quantitate either spontaneous or therapeutically induced changes in disease activity.