Exocytosis is the primary means of cellular secretion. Because exocyto
sis involves fusion between the plasma membrane and the membrane of se
cretory vesicles, it is likely that proteins on these two membranes, a
s well as additional proteins in cellular cytoplasm, mediate exocytosi
s. Although we know much about the proteins of secretory cells, we sti
ll have much to learn about how these proteins participate in exocytos
is; in no case has an unambiguous exocytotic function been assigned to
any of these proteins. To identify the roles of proteins in exocytosi
s it is necessary to perturb protein function in living secretory cell
s. We review a number of perturbation strategies and summarize what th
is approach has taught us about the functional roles of proteins in ex
ocytosis, concluding with a molecular model of protein dynamics during
exocytosis.