In an attempt to study the generality of effect of donor-specific blood transfusions (DSBT) in inducing immunologic unresponsiveness, the survival rates of heart, pancreas, and skin allografts were compared in blood-pretreated animals. DSBT, when given in a single-dose or multiple-dose protocol, prolonged cardiac allograft survivals in some strain combinations (F----L, LBN----L), but not in others (BN----L, ACI----L, ACI----WF). Antilymphocyte serum further prolonged survivals in protocols in which blood pretreatment was effective, and proved capable of reversing a state of sensitization in rats treated with multiple small-volume transfusions. In no case did the protection afforded the cardiac allografts extend to pancreatic or skin allografts, even with the use of nonspecific immunosuppression and a weak histocompatibility barrier. Third-party cardiac allografts were not protected by the blood pretreatment, attesting to the specificity of the transfusion effect. Addition of azathioprine during the blood pretreatment neither interfered with nor significantly improved the results seen with transfusion alone. The graft prolongation that follows blood pretreatment appears to be influenced by many factors, such as donor-host histocompatibility, the specific tissue transplanted, the blood transfusion schedule, and the use of adjunctive immunosuppression--but presently it is an unpredictable phenomenon.