Spontaneous viral leukemia, occurring in AKR mice starting at 6 mth, is thymus-dependent, and can thus be abrogated by thymectomy. Two components of the thymic stroma, insoluble thymic fraction (ITF) and soluble thymic factor (STF) previously shown to induce sequential steps in T-cell differentiation, were investigated for their role in the triggering of leukemia. AKR mice, thymectomized at 1 mth received weekly injections of either ITF, STF, ITF + STF or control splenic fractions, and deaths by leukemia were recorded. Mice having received ITF all died at approximately the same rate as the sham-thymectomized untreated controls, while only 20% of the ITF + STF treated mice died. Untreated, STF- or splenic fractions-treated controls all survived. These results are interpreted as indicating that ITF induces a T-cell population sensitive both to leukemic transformation and to STF-mediated differentiation.