Four different antineuronal autoantibodies have been identified in 23 of 47 patients with paraneoplastic cerebellar degeneration (PCD). The most common, an antibody against 34- to 38-kDa and 62- to 64-kDa protein antigens in the cytoplasm of Purkinje cells, was found in 18 patients. It is a highly specific marker for a severe stereotypical subacute pancerebellar syndrome of truncal and appendicular ataxia, dysarthria, and nystagmus in women with cancer (usually ovarian or breast carcinoma). Different anti-Purkinje cell antibodies (APCA) were found in 2 other patients with PCD. With two possible exceptions, an APCA was not found in patients with other neurological diseases, with cancer not associated with neurological symptoms, or in normal subjects. Antibodies reactive with neuronal nucleoproteins were identified in 3 other patients with PCD: an antibody that recognized 35- to 40-kDa neuronal antigens was found in 2 women with small-cell lung carcinoma, while an antibody in a woman with breast carcinoma identified 53- to 61-kDa and 79- to 84-kDa antigens. Detection of an antineuronal antibody in a patient without known cancer should prompt a careful search for a tumor at a site appropriate to the antibody type.