It has been well established that the volume of secretory vesicles can be m
odulated. However, we present the first data demonstrating that the amount
of transmitter in a vesicle can regulate its volume. Amperometry and transm
ission electron microscopy have been used to determine that L-3,4-dihydroxy
phenylalanine and reserpine increase and decrease, respectively, the volume
of single pheochromocytoma cell vesicles as well as their catecholamine co
ntent. Because changes in vesicular catecholamine content are tracked by ch
anges in vesicle volume, our results indicate that when quantal size is alt
ered via the vesicular monoamine transporter the concentration of catechola
mines within the vesicles remains relatively constant. This previously unid
entified cellular response provides new insight into how catecholamines can
be packaged in and released from secretory vesicles.