In rats, injection of nickel sulfide (5 mg) into each pole of one kidney, unlike intramuscular administration, elicits a plethoric condition a few weeks later. The resulting hematologic changes (increased hematocrit, hemoglobin, erythrocytes and circulating erythrocyte mass with normal plasma volume) indicate that the plethoric condition is due to polycythemia, which is not associated with alterations in the 2,3-diphosphoglyceric acid content of erythrocytes. Removal of the treated kidney, following the development of the polycythemia, as well as the tumor growth and expansion in the renal parenchyma, reverse the plethoric condition, suggesting that the erythropoietic changes derive from nickel-induced renal lesions. Further studies are required to elucidate the nature and mechanisms of the cellular alterations.