The clinical investigations of Hodgkin's disease (HD) in adults and children described in this application include four clinical trials which are largely based upon the cumulative knowledge of therapeutic efficacy and early and late effects of treatment of approximately 2200 patients with HD at Stanford University over a 30 year time span. In addition, plans to continue the followup of patients participating in previous clinical trials, documentation of the complications of therapy and maintenance of a large database are described. The overall objectives of the adult and pediatric clinical protocols have a striking symmetry: refinement of treatment as a function of stage and tumor burden, and further minimization of early morbidity and/or late complications of therapy. There are four clinical protocols: one each for favorable, limited stage HD in adults and children and one each for unfavorable (bulky or advanced stage) HD in adults and children. Each of the protocols tests a novel chemotherapy combination which uses drugs and cumulative doses selected to avoid pulmonary and cardiac dysfunction, sterility and leukemogenesis. In adults, the increased dose intensity of the chemotherapy for unfavorable disease is anticipated to increase the efficacy while allowing abbreviation of the duration of therapy. In children, the novel chemotherapy is anticipated to result in similar, excellent cure rates, but will increase survival in the reduction of fatal late effects. Radiation therapy is used more sparingly than in previous trials in order to reduce late effects, which include second malignancy in adults and soft tissue and bone growth in children. Specifically, children receive low dose irradiation to involved fields. Adults with favorable, limited disease receive reduced volume irradiation made possible through the use of a minimally toxic chemotherapy (in a randomized trial compared to standard extended field irradiation), while adults with extensive disease receive irradiation only to initial bulky or residual disease. All patients participating in these studies will be clinically staged such that the attendant risks and morbidities of laparotomy and splenectomy will be avoided. An important part of this application is the continued followup of patients enrolled on prospective clinical trials at Stanford University since 1962 for endpoints of survival, from relapse and documentation of the long term effects of therapy. This includes the description of the long-term morbidity, fatal treatment communications, causes of death and survival in over 2200 patients with HD treated at Stanford University. Prospective evaluations of cardiac and pulmonary function, growth and fertility which began in 1980 will continue. These data are maintained in a sophisticated databank, representing a national resource for the efficacy and complications of treatment of HD.