An account of the chromosome damage found in the lymphocytes of thirteen patients who had received injections of gold-198 into knee joints was reported in a preliminary communication (Stevenson, Bedford, Hill, and Hill, 1971a). There were great differences in the amount of damage which followed injections of the same amount of activity in these patients. However, the mean level of damage appeared too high to be explained by the assumption either that it occurred as a result of irradiation of lymphocytes in the injected joint, or that the radionuclide was distributed throughout the whole body, for the average radiation dose to the body would only be about 0 5 rad from the gamma radiation per mCi of gold-198. It was suggested that the high level of chromosome damage in lymphocytes relative to the amount of activity injected was most probably due to the movement of gold from the knee along the lymphatics to the inguinal lymph nodes, where enormous numbers of lymphocytes in transit through the nodes would come within the range of the beta emission of the radionuclide.Many patients have been treated with benefit by gold-198 or yttrium-90 intra-articular injections (Ansell, Crook, Mallard, and Bywaters, 1963;Delbarre, Cayla, Menkes, Roucayrol, Ingrand, and Aignan, 1969; Bridgnan, Bruckner, and Bleehen, 1971), and it seemed important to try to assess more accurately the amount of chromosome damage in lymphocytes in order to attempt to elucidate the prognostic significance, if any, to patients from these procedures. For this reason, and because there is very little available information on the cytogenetic effects of parenterally-administered radioactive isotopes in man, it was decided to investigate further cases.Including those reported in the preliminary paper, 48 patients who have had gold-198 injections, and 22 who have had yttrium-90 injections have now been investigated. None of these patients received any external radiotherapy. As the appendices show, blood samples from some patients were not taken until several months or years after the injections. Some were taken both before and at intervals after treatment, and some patients were scanned after injection in order to determine the distribution of the isotopes.The colloidal gold-198 (half life 65 hrs) and yttrium-90 (half life 64 hrs) were obtained from the Radiochemical Centre, Amersham, catalogue numbers GCS1P and YAS3P respectively.The gold preparation is a colloidal suspension of metallic gold stabilized with gelatin and with particle sizes of up to 20 pm. Most of the activity is in the 10-13 pm particles. The yttrium preparation is ionic yttrium bound to a colloidal ion exchange resin with a particle size range from 20 to 50 pum.