Tilorone is a synthetic amino-alkoxyfluorenone with demonstrated antiviral and antitumor properties. This study gives evidence for immunosuppressive properties of the substance as well. Buffalo rats (AgB6) received skin grafts from rats of the Fischer (AgB1) strain. Control animals rejected in 9.9 +/- 1.1 days, compared to 13.7 +/- 2.3 days for recipients treated with Tilorone. Steroids when combined with Tilorone further prolonged skin allografts to 16.7 +/- 2.6 days. Heart allografts from Fischer (AgB1) and Brown-Norway (AgB3) to Lewis (AgB1) also were performed. In the Fischer to Lewis combination, allograft survival was prolonged from 14.7 +/- 1.0 to 31.0 +/- 3.8 days. In the Brown-Norway to Lewis combination, treated rats rejected in 10.2 +/- 1.4 days versus 6.6 +/- 1.1 days for controls. Increased levels of cytotoxic antibody specific to lymphocytes of the donor strain were noted in Tilorone-treated animals. The mechanism by which Tilorone prolongs allografts may well involve a combination of interferon production and specific suppression of thymus-derived lymphocytes.