Using the changes in several blood parameters and in the histological picture of the liver as markers of toxicity, the effect of hydroxyurea (HU) in healthy rabbits or mice was examined during two weeks after a single administration of this drug. In rabbits a transient significant decrease in blood erythrocyte count with a gradual increase in their osmotic resistance, a suppression of granulocyte phagocytic capacity, and an elevation of acid phosphatase activity in the serum were found. An increase in the proportion of lymphocytes without detectable lysosomes as tested by supravital staining also appeared. No significant difference was observed in the white cell count and lipoperoxide levels after HU administration. Histological picture of the liver, excised from HU-treated mice, indicated a marked hepatotoxicity of the drug. Some of the toxic effects were reduced in animals supplemented with vitamins E and C.