The formation of constitutive secretory vesicles and secretory granules from the trans-Golgi network is inhibited by brefeldin A, suggesting a role for ADP ribosylation factor and other coat proteins in the budding process, and is regulated by multiple heterotrimeric G proteins. Membrane proteins are sorted to secretory granules through signals in their cytoplasmic domains and, like secretory proteins, by aggregation of their lumenal domains. Synaptic vesicle membrane proteins undergo exocytotic-endocytotic recycling before synapse formation, consistent with the proposed biogenesis of synaptic vesicles from early endosomes.