Survival rates for many of the childhood and adolescent cancers have improved at a remarkable pace over the past 35 years. With this success has come the need and responsibility to consider the long-term morbidity and mortality associated with the treatments responsible for the increases in survival, the resource represented by the Childhood Cancer Survivor Study (CCSS) is the result of a multi-institutional collaboration and represents the single most comprehensive body of information ever assembled on the health status of long-term survivors. CCSS has successfully established and followed 14,370 five-year survivors of childhood and adolescent cancer diagnosed between 1970-1986 and a sample of 3,737 sibling controls. CCSS participants, derived through 26 participating clinical centers, have been characterized relative to cancer diagnosis, therapy received and health and quality of life-related outcomes encompassing over 248,000 person-years of follow-up. CCSS has established an effective organizational structure to direct the scientific and administrative functions of this unique resource. The CCSS resource has been utilized by investigators from a broad range of disciplines, including inquiries from 82 investigators new to CCSS, with 56 subsequently becoming involved in research initiatives. As a resource, CCSS produced 41 peer-reviewed publications during current funding period and has been the source of 14 investigator-initiated projects with independent funding in excess of $9,000,000 from NIH (n=6) and non-governmental agencies/foundations (n=8). The objectives of this competitive renewal are to: (1.) maintain the strong and productive resource of the CCSS through continued follow-up of the initial population, diagnosed between 1970-86;(2.) enhance the CCSS resource by recruiting 14,800 5-year survivors diagnosed between 1987-99 and 4000 sibling controls;and, (3.) promote and facilitate the use of the CCSS resource including the study participants, as well as data and biological samples previously collected for investigator-initiated studies that address important questions relating to childhood cancer survivors. Within the framework of defined guidelines and procedures, aggressive new initiatives will be undertaken to increase access/utilization of CCSS as a resource by (a) markedly increasing visibility through publications, presentations at national/international meetings, links with websites, direct marketing, and establishment of liaisons with professional societies;and (b) implementing an innovative strategy of establishing a comprehensive public-use data set. CCSS provides a dynamic framework and resource to investigate current and future questions among childhood cancer survivors.