Dermal exposure of rabbits to cyclohexanone oxime (CHO) for 24 hr at 0, 0.8, 2, and 5 g/kg caused dose-related reticulocytosis on the day after dosing as well as a decrease in hemoglobin in the 5-g/kg females 7 days postdosing. Gavage of rats 5 days a week for 13 weeks at levels of 0, 0.25, 2.5, and 25 mg/kg resulted in a dose-related decrease in erythrocyte number, hemoglobin, and hematocrit, with an accompanying increase in circulating reticulocytes and nucleated erythrocytes, in both sexes. Also seen were corneal opacities and an increased incidence of Howell-Jolly bodies. Results suggested an increased erythropoiesis in the spleen and bone marrow. The data from satellite groups terminated at 30 and 60 days revealed no effect at the lower test level, but results from the end of the study showed a clear cumulative dose response down to the 0.25-mg/kg level. Males were affected earlier and at lower doses than females. These results, along with those of a subacute study with a recovery period, suggest that CHO induces an oxidative attack on erythrocytes which appears reversible upon cessation of exposure.