Allograft tolerance occurs in rodents given a dose of antilymphocyte serum (ALS) and intrathymic injection (ITI) of donor splenocytes (SC) 1–3 weeks prior to transplant (TX). The purpose of our study was to test total lymphoid irradiation (TLI) as an alternative to ALS in ITI tolerance induction to heart, islet, and skin allografts. Prepubertal Wistar Furth rats were recipients. ITI of donor (Lewis) SC was done at the end of the TLI course. Rats received either a heterotopic heart, a skin graft, or 2300 islets (diabetic recipients) intraportally from Lewis donors. TLI (without ITI) in a dose of 200 rads/day for 5 consecutive days, followed by TX in 3 weeks resulted in indefinite acceptance of heart (but not islet or skin) grafts in 60 % of the recipients. These data indicate that TLI by a dose schedule of 200 rads/day for 5 days should be tested for clinical relevance in large animal recipients of immediately vascularized grafts.