The immunochemical and functional properties of IgG fractions from patients with Lambert-Eaton myasthenic syndrome (LEMS) were examined in chick and rat synaptosomes. LEMS IgG immunoprecipitated 125I-omega conotoxin GVIA (125I-omega CgTx) labeled N-type calcium channels solubilized from both tissues, and reacted with a 65 kDa protein band in immunoblots of rat synaptosomes. Depolarization-induced 45Ca2+ influx into chick synaptosomes was partially inhibited by omega CgTx, whereas influx into rat synaptosomes was insensitive to omega CgTx. No effect of LEMS sera or IgG on 45Ca2+ uptake was apparent in either preparation.