Healthy A/J mice grafted with either BALB/c or C57BL/6 tail skin routinely reject these grafts with a mean survival time (MST) of 12-14 days. Low dose cyclophosphamide, Cy (50 mg/kg) on the day of engraftment can enhance survival of both grafts (MST 17-20 days). If mice are given three weekly intravenous injections of BALB/c peripheral blood prior to grafting, specific enhancement of BALB/c but not C57BL/6 grafts results (MST 18 and 12 days, respectively). Mice given several ip treatments with Cy in association with a novel taste (saccharin, Sacc) in their drinking water also show a conditioned immunosuppression if subsequently exposed to Sacc alone. Such mice given BALB/c or C57BL/6 skin grafts and re-exposed to Sacc also show prolonged survival of these skin allografts (MST 16-17 days). If conditioned mice are also treated, by pretransplant donor-specific transfusion, to develop a state of specific suppression of allograft immunity, then subsequent grafting with BALB/c or C57BL/6 grafts coupled with re-exposure to Sacc lead to a further prolonged survival of grafts specifically in the BALB/c mice (MST 29 days).