The resolved α-GTPγS (α*) and βγ-subunits of human erythrocyte G k , the stimulatory regulatory component of hormone-responsive K + channels, were tested for their potential stimulatory activities on the K + channel of the endocrine GH 3 cell. Concentrations as low as 0.5 pM α k * consistently activated K + channels in isolated membrane patches, and saturating effects were obtained with 50 pM α k *. In contrast 2000-4000 pM βγ was without effect. We conclude that G k acts on K + channels through its α-subunit in a manner akin to that of G s acting on adenylyl cyclase and transducin acting on cGMP-specific phosphodiesterase of photo-receptor cells.