Naive CBA mice injected with AKR spleen cells via the portal vein (p.v.) subsequently showed decreased stimulation in vitro in a primary MLR or cell-mediated lympholysis assay with irradiated AKR stimulator cells. No inhibition of stimulation by B10.BR cells is seen. These mice also show specific prolongation of survival of AKR skin grafts in vivo and diminished capacity for in vivo priming for (secondary) anti-AKR responses in vitro. These effects are not seen if initial challenge is with AKR cells injected subcutaneously (s.c.) or via the lateral tail vein (i.v.). Moreover, if immune CBA anti-AKR mice are similarly challenged with AKR cells via the portal vein, no suppression of anti-AKR immunity is elicited, as determined by subsequent in vitro assays or in vivo graft rejection. However, spleen cells from CBA anti-AKR immune mice can be used to induce, in further naive CBA mice, a specific suppression of subsequent anti-AKR graft reactivity (assayed in vitro or in vivo). Active T cell-mediated suppression can be documented using both these protocols though the additional involvement of specific serum-mediated suppression cannot be eliminated.