The National Institute on Aging Interventions Testing Program (ITP) was developed to: 1) provide a standardized program for preclinical evaluation of the efficacy of interventions aimed at prolonging health-span and/or life-span; 2) to provide the NIA with a mechanism to evaluate possible health dangers of purported, but untested, "anti-aging" treatments; 3) candidate treatments emerging from these preclinical studies can then be recommended for clinical evaluation. Key features of the program include the use of genetically heterogeneous mice (a standardized four-way cross) and replication at three test sites (The Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas, UT). Proposals are solicited from potential collaborators annually. Criteria for the efficacy of candidate interventions on aging include measures of increased median and/or maximum lifespan, delays in onset and reduced incidence of age-related pathology, and preservation of physiological and/or behavioral function into late life. Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen (NFP), 4-OH-alpha-phenyl-N-tert-butyl nitrone (4-OH-PBN), or nordihydroguiaretic acid (NDGA). A planned interim analysis was conducted using survival data available on the date at which at least 50% of the male control mice had died at each test site. There were significant differences between centers in survival of control males, at the interim time point; survival of control females did not differ between sites. Males in the NDGA group had significantly improved survival (p=0.0004), with significant effects noted at TJL (p<0.01) and UT (p<0.04) and a non-significant trend at UM. None of the other agents altered survival, although there was a suggestion (p=0.07) of a beneficial effect of aspirin in males. An analysis is planned when 90% of the mice have died, but the current data show that NDGA reduces early life mortality risks in genetically heterogeneous mice at multiple test sites.