EXPERIMENT AL OAT A on the immunosuppressive capabilities of various preparations of anti-lymphoid cell sera and globulins have been accumulating since Metchnikoff's documentation in 1899 of the capacity of heterologous antisera to destroy leucocytes. Worldwide interest in the potential applicability of this model to transplantation was stimulated by the experiments of Woodruff and his associates at Edinburgh and by Medawar's studies in London, in the mid-twentieth century. The exciting data originating from these and other laboratories on the clear-cut and reproducible effects of heterologous antisera in attenuating allograft rejection responses provided a basis for Starzl 's pioneering efforts in 1966 to extend the results of animal studies to human kidney transplantation. Since then, the clinical use of heterologous anti-lymphocyte globulins (ALG) in transplantation has been the subject of intensive scrutiny at many leading transplantation centers throughout the world. Such studies have been done under a wide spectrum of different experimental conditions, and with continuing uncertainty and disagreement on the actual role and contributions of ALG to clinical transplantation. Some of the difficulties of interpretation which appear to continue to reign in the field are reflected in the views of ALG presented in this issue by two leading international experts on ALG, Drs. Mark A. Hardy, of New York, N.Y., and Anthony P. Monaco, of Boston, Mass. Dr. Hardy, who represents the true believer's stance, is generous in his praise of ALG, in all its forms and expressions, but balances his judgment with a highly realistic, and on occasion, almost grim recognition of the shortcomings of ALG as he notes, ALG is indeed /lot a panacea, akin to Ehrlich's magic bullets. On the other hand, Dr. Monaco, who undertook the difficult task of defining some of the problems associated with ALG, presented such problems in the light of the more beneficial effects of these agents, and emphasized the enormous research opportunities provided by ALG's current clinical shortcomings. It is difficult indeed to emerge from the elegant overview of the field provided by Drs. Hardy and Monaco without suspecting that not all is well in the world of ALG. In many ways, it resembles a strikingly beautiful painting which is as yet unfinished, and where a few key colors are still missing. The capacity of well-defined ALG preparations to prolong allograft survival in experimental animals, under precisely defined conditions, has become established beyond any reasonable doubt. Extension of the use of ALG to the human situation has been difficult, however, because of the almost innumerable and on occasion unknown variables which can potentially bedevil efforts in clinical investigation. Drs. Hardy and Monaco describe the problems in extenso, and point to some possible approaches designed to avoid at least some of the more evident variables. There appears to be general agreement that truly immunosuppressive batches of ALG (regardless of the heterologous animal species used to prepare the antisera) can indeed ameliorate the early course of human kidney transplantation (first year). Such active ALG's are also effective in the management of rejection crises, and appear to be remarkably free of side effects, beyond chills and fevers, intermittent skin rashes, and occasional joint pains. Leukopenia and thrombocytopenia have occurred in only lOo/e of cases. On the other hand, it is still not clear that ALG treatment does exert a significant effect upon the long-term fate of the kidney allograft in man. Dr. Monaco notes in this regard that the overall beneficial effects of ALG may not be great enough (10* 15* improvement in the results) to attain significance particularly in view of recent improvements in the results due to other factors, such as blood transfusions, for example. Assessment of the statistical significance of the role of ALG in this regard would require