To determine whether titers of anti-P/Q type and anti-N type calcium channel antibodies provide distinct information, both types of assay were performed during follow-up of 7 patients with Lambert-Eaton myasthenic syndrome (LEMS). In 4 patients with both antibody responses, titers evolved independently and often in an inverse relationship. Two patients with squamous cell lung carcinoma (SqCLC) produced anti-N type channel antibodies, but no detectable anti-P/Q channel responses. These results suggest that anti-N channel autoantibodies constitute an immune response distinct from the anti-P/Q type channel specificity and can also correlate with clinical evolution. Consequently combined assays may provide more comprehensive information during follow-up of LEMS.