We speculated that IgG from patients with Lambert-Eaton myasthenic syndrome (LES) would inhibit calcium-dependent hormone secretion in rat anterior pituitary (AP) cells. Primary cultures of normal AP cells were continuously exposed to crude IgG from an LES patient or from healthy control subjects, and the incubation media were assayed for prolactin (PRL) or growth hormone (GH). The LES IgG caused a time- and concentration-dependent reduction of PRL and GH release compared with control IgG over 0.5 to 48 hours using concentrations of 0.01 to 4.0 mg/ml. The calcium-channel activator maitotoxin stimulated 45Ca2+ uptake and PRL release from AP cells under control conditions, and the LES IgG significantly reduced both actions of maitotoxin. Thus LES IgG appears to modulate an AP antigenic site, perhaps representing an integral component of voltage-gated calcium channels that may share properties with similar presynaptic elements at the neuromuscular junction.