Abstract: Harringtonine (HA) and homoharringtonine (HO), two new antileukemic agents, were submitted to toxicological studies in mice, rabbits and dogs. The major target organs involved in toxicity in rabbits and dogs produced by 5 or 7 day treatments with either alkaloid were limitted to G. I. tract, heart and hematopoietic organs. Most deaths were attributable to cardiac dysfunction. After injection of lethal doses, hepatic and renal toxicities of mild to moderate degree occurred only in individual cases. When such treatments were repeated for two additional courses, no additional significant toxicity was observed. However, the cardiac and hematopoietic toxicity appeared to be moderately cumulative. All toxicities observed were dose-dependent, predictable and completely reversible upon discontinuation of treatment. No significant delayed toxicity was noted during an observation period of 6 weeks or more. Neither inter or intraspecies nor sex related differences in qualitative toxicity of either HA or HO were observed. 0.42 mg/kg/d×5 of HA and 0.16 mg/kg/d×7 of HO were established as the toxic doses high for dogs. The LD₅₀ S (±S·E) of HA and HO in mice (I. P.) were found to be 4.17±0.30 and 3.17±0.19 mg/kg, respectively. Although He was found to be more potent than HA, qualitatively the two alkaloids did not differ significantly.