Paraneoplastic limbic encephalitis (LE) is considered a particular manifestation of paraneoplastic encephalomyelitis (PEM), a remote effect of cancer almost always associated with anti-neuronal antibodies (anti-Hu; also called ANNA 1) and small cell lung carcinoma (SCLC). In order to define the frequency of anti-Hu antibodies in LE with SCLC and to analyse possible clinical differences between patients with and without anti-Hu antibodies, the charts of 16 patients with LE and SCLC were reviewed. Eight patients (50%) had anti-Hu antibodies (anti-Hu+) whereas eight patients (50%) had no detectable anti-neuronal antibodies (anti-Hu-). The clinical and laboratory features of LE and time to diagnosis of SCLC were similar in the anti-Hu+ and anti-Hu- groups. Involvement of other areas of the nervous system compatible with the diagnosis of PEM was observed in seven (87.5%) patients of the anti-Hu+ group but in only one (12.5%) of the anti-Hu- group (P = 0.012). Five patients, including four of the anti-Hu- group, had a partial improvement of the LE after treatment of the SCLC. Another anti-Hu- patient improved spontaneously. Six patients of the anti-Hu+ group died from the neurological disorder, whereas in the anti-Hu- group the cause of death was progression of the SCLC in the three patients who died. The results of this study indicate that the absence of anti-Hu antibodies does not rule out the presence of an underlying SCLC in patients with a clinical diagnosis of LE. Patients with LE and SCLC who are without anti-Hu antibodies are less likely to develop PEM and seem to improve more often after treatment of the cancer than those who present anti-Hu antibodies.