We have characterized age-related thymic atrophy in the guinea pig, including identification of antibodies that allow immunohistochemical assessment of thymopoiesis. Age-related thymic atrophy in guinea pigs more closely resembles what occurs in humans histologically and in thymus weight, cellularity, and percent functional area than do other rodent models. The guinea pig model is thus particularly well-suited to study the role of the thymic perivascular space in age-related thymic atrophy. We next tested the hypothesis that dietary supplementation with Vitamin C could prevent or delay age-related thymic atrophy. Thymus histology, weight, cellularity, and percent functional area did not differ at 12 months between groups that received 3, 30, or 150 mg Vitamin C daily from 4 months of age. Thus long-term supplementation with up to 130 mg/kg/day Vitamin C is insufficient to influence the time course and extent of age-related thymic atrophy in guinea pigs, (C) 2001 Elsevier Science Ltd, All rights reserved.