Three cases of hypercalcemia were recognized among 11 cats presenting with leukemia-lymphoma for ex vivo immunoadsorption therapy using Staphylococcal Protein-A-coated filters. In addition, the initial mean serum calcium concentration of cats with leukemia-lymphoma was significantly higher (P less than 0.005) than that of healthy control cats or feline-leukemia-virus-infected cats without malignancy. During immunotherapy of the hypercalcemic cats, objective reduction in the extent of the malignancies was associated with a small reduction in the serum calcium concentrations. This response to treatment, the lack of skeletal metastasis, and the absence of renal and parathyroid pathologic findings imply that humorally mediated mechanisms may have been responsible for the production of the hypercalcemia.