The distribution of terminal deoxynucleotidyl transferase (TdT) peak I and peak II in thymuses and peripheral lymphoid tissues was examined in a variety of mouse strains in relation to tumor burden and age. TdT peak I was found to be present in all strains at comparable levels, which did not change with age. TdT peak II levels were also comparable for the strains examined at 1 week of age. In contrast to peak I, however, in NIH Swiss and AKR mice, peak II activity decreased rapidly at 2 weeks of age and by 6 weeks of age less than 2% of the initial activity remained. In C57BL/6 mice there was a similar loss of peak II activity with age although this change started at about 4 months of age and by 8 months of age approximately 15% of the initial activity remained. These changes did not appear to be due to the presence of an inhibitor. Leukemic C57BL/6 and AKR mice were also examined for TdT. Both strains characteristically had TdT peak I in peripheral lymphoid tissues infiltrated with transformed thymocytes. AKR mice had only TdT peak I in the thymus, whereas C57BL/6 thymuses had both peak I and II at levels comparable to age-matched controls. No aberrant distribution of TdT was observed in a spontaneous reticulum cell sarcoma or Rauscher MuLV-induced erythroblastosis.