We studied serum autoantibodies from six patients with paraneoplastic cerebellar degeneration using rat brains. Immunohistochemically, serum samples from four of six patients with uterine or ovarian tumors showed a similar staining pattern, labeling Purkinje cells and various other neurons distributed throughout the brain and spinal cord. The immunoblot study showed that these serum samples recognized the common 52-kd band. Serum from a patient with duct carcinoma of the breast reacted with the 46-kd band with a similar but weaker immunohistochemical reactivity. Serum from another patient with small-cell carcinoma of the lung in whom paraneoplastic cerebellar degeneration and Eaton-Lambert myasthenic syndrome developed recognized the 40-kd and 38-kd bands with a different immunostaining pattern. Autoantibodies in patients with paraneoplastic cerebellar degeneration are directed to a variety of neuronal antigens that may differ from patient to patient.