Among the proteins regulating vesicular traffic, the small, Ras-like GTPases have received particular attention. Several recent reports indicate that another class of GTP-binding (G) protein, the heterotrimeric G proteins, also participates in the regulation of vesicular traffic. Thus, studies using transfected cells and cell-free systems show that a pertussis toxin-sensitive trimeric G protein, G(i3), is involved in the formation of secretory vesicles from the Golgi complex. These results raise the intriguing possibility that signal transduction processes across intracellular membranes play a role in vesicle formation, and provide important clues about the molecular machinery involved in this process.