The SNARE proteins including syntaxin, SNAP-25 and VAMP, play an essential role in membrane fusion events such as those that occur during exocytosis to allow fusion of secretory vesicles with the plasma membrane and the release of vesicle contents to the exterior of the cell. Many other proteins are involved in the regulation of the events that trigger and mediate vesicle fusion and amongst these are members of the Sec/Munc and Rab protein families. In regulated exocytosis of synaptic vesicle and dense-core granules Munc18-1 and Rab3A are known to be important but their exact functions remain to be elucidated. Both Munc18-1 and Rab3A have been implicated in vesicle docking at the plasma membrane. We have used PC12 and adrenal chromaffin cells expressing various forms of these proteins to investigate the timing and sites of their action. Expression of mutated forms of Munc18-1 coupled with biochemical analysis of their protein-protein interactions and analysis of the kinetics of exocytosis has allowed us to establish syntaxin-dependent and syntaxin-independent roles for Munc18-1 that affect both early (recruitment and docking) and late stages (exocytosis dynamics) of exocytosis. In addition, we have been examining dynamic aspects of Rab3A on secretory granules using confocal microscopic imaging of GFP-tagged Rab3A in live cells. One of our major goals is now to understand how Munc18-1 and Rab3A interact to control exocytosis.