On a weight basis many radionuclides must be viewed as among the most toxic agents known. For this reason and because of the potential of ionizing radiation to produce long-term effects both somatic and genetic, a very large amount of work has been done. In a sense our knowledge of these agents is almost out of proportion to the numbers of human beings affected directly, except for the ubiquitous exposure to nuclides from fall-out. For this reason the current tendency to put radiation hazards in perspective with other hazards, particularly in considering environmental pollution, is laudable (I). However, knowledge gained with radiation and radioisotopes is proving very useful to other areas of toxicology. Hence this review is directed primarily to the pharmacologist­ toxicologist rather than to the specialist in radiation biology. Radionuclide toxicology has not been covered in this Annual Review series since that of Catsch, in 1963 (2). In the interim, a veritable flood of new work has been completed, much of it the result of experiments and programs begun many years before. Fortunately, there is an abundance of reviews, symposia, and monographs (3-17), but except for the monograph of Spiers (3), none appear to have had a charter to consider the entire field. A large compendium on uranium, plutonium, and the trans-plutonic elements (18), should be available at about the same time as this review, and certain of its chapters are referenced specifically in these pages for more details. Because of space limitations, I have had to be highly selective and frequently somewhat superficial. Some entire areas have been omitted (e.g., biochemical effects, instrumentation, nuclear medicine, therapy of radionuclide deposition), others given short shrift (e.g., "metabolic" patterns, fetus and newborn, inhala­ tion problems) and American work has been described in more detail both be­ cause I know it better and, except for Soviet and UK work, it is most extensive. Emphasis is placed on carcinogenesis, dose-response relations and dosimetry, and environmental aspects of the general problem including references to the "nuclear power controversy." Work completed during the last five years in each area is given priority but even so, drastic selection has been essential.