Immunosuppressive effects of newly developed synthetic progestins, melengestrol acetate (MGA), and 3 pyrimidine analogs, ara-cytidine (Ara-C), Ara-C 5''-benzoate and octanoate, were investigated on the heart allograft survival in the rat. MGA at the dose of 25 mg/kg given every 3rd day starting 1 day before the grafting through day 20 prolonged the graft survival significantly without toxic effects (80.2 .+-. 40.2 days vs. control 7.0 .+-. 0.1 days). The high dose (50 mg/kg/day)was more effective (137.4 .+-. 26.6 days), but a high incidence of multiple abscesses (37%) was also noted. The other 3 agents were highly toxic or not immunosuppressive.