Several immunologic procedures are described, by which the postthymectomy autoimmune thyroiditis in (C3H/HeMs X 129/J)F1 female mice was clearly prevented. These include the grafting of a neonatal thymus or a cell injection from adult thymus, spleen, and lymph nodes, but not from bone marrow. Their preventive effects, however, depended on the timing of treatments. In general, the earlier the treatment was given, the better the effect was. Thymus cells from 7-day-old mice were effective, whereas spleen cells from the same donors and neonatal thymus cells were ineffective. Neonatal thymectomy or 500-rad irradiation decreased the number of effective cells in the spleen. All of these data suggest that the cells responsible for the prevention of postthymectomy thyroiditis are T-cells, and that ontogenetically these cells first acquire their preventive ability in the thymus after birth and then migrate to the peripheral lymphoid tissues. The minimal effective dose of adult spleen cells was 15 X 10(4). Although 10(7) spleen cells from the mice thymectomized 3 days after birth failed to prevent the disease, the same dose of cells from those thymectomized at 7 days clearly prevented it. This suggests that qualitative rather than quantitative differences exist in peripheral T-cells of mice thymectomized 3 days after birth and those of normal mice or mice thymectomized at 7 days when the animals get to adulthood.