Circulating thymic hormone activity and thymic histology were studied in patients undergoing open heart surgery. Plasma thymic hormone activity was measured using a bioassay based upon thymocyte antigen induction on null mouse lymphocytes. Activity was highest at 15-30 yr of age and declined thereafter, being negligible after the sixth age decade. The age-related decline of circulating thymic hormone activity correlated, in general, with progressive thymic involution. However, hormone activity was detected in plasma from some cases with advanced involution, suggesting that the normal young thymus may have considerable functional reserve.