Neurosecretory vesicles of paraventricular corticotropin releasing factor (CRF) neurons increase in size after adrenalectomy (ADX) in parallel with an augmentation of their content in vasopressin (VP) immunoreactive sites. We have investigated in the Brattleboro rat model whether changes in vesicle size are related to elevated intravesicular concentrations of VP. Using quantitative immunoelectron microscopy, VP and CRF immunoreactive sites were assessed in the dense core vesicle compartment of CRF axon terminals in the median eminence. In heterozygous (control) rats, CRF was co-packaged with VP, and ADX induced a 3-fold increase in VP labeling intensity and produced a significant increase in the vesicle diameter. In homozygous rats lacking VP, only CRF immunoreactivity was detectable, and ADX was not accompanied by an increase in vesicle size. These observations suggest that the presence of VP is necessary for the ADX induced increase in vesicle size and that this increase might be needed to accommodate the excess of VP in the vesicle space.