We previously reported exocytotic release events of noradrenaline and adrenaline (N/A) in organotypic brainstem slice cultures from young (pre-hypertensive) spontaneously hypertensive rats (SHR) and normotensive Wistar (WR) controls. The distribution of quantal N/A sizes suggested diameters of up to 300 nm or more for a minority of vesicles, decidedly larger than described in earlier publications (Chiti & Teschemacher, 2007). Release quanta were significantly larger in the rostral ventro-lateral medulla (RVLM) of SHR as compared to the nucleus of the solitary tract (NTS) of SHR; quantal events were also significantly larger in RVLM of SHR than in NTS or RVLM of WR (Teschemacher et al., 2008). In the present study, we employed transmission electron microscopy in combination with immunogold labelling for dopamine-β-hydroxylase (DbH) or vesicular monoamine transporter-2 (VMAT2) to measure diameters of N/A-containing (NAergic) vesicles in neurones in the NTS and RVLM of adult WR (n=3) and SHR (n = 3). Experiments were conducted according to the UK Animals (Scientific Procedures) Act 1986 and associated guidelines. 129 NAergic vesicle cross sections were evaluated and the distribution of vesicle diameters was extrapolated by linear regression analysis. The data indicate that the majority (>95%) of labelled vesicles have diameters of more than 150 nm and some measure up to 500 nm. Vesicle size distributions were neither significantly different between NTS and RVLM of WR, nor between NTS in WR and NTS in SHR (Student unpaired t-test). In contrast, the vesicle diameter distribution in RVLM of SHR (median 294 nm) was right shifted as compared to RVLM of WR (median 204 nm; p<0.01) and as compared to NTS of SHR (median 215 nm; p<0.001). Double immunogold labelling showed that, in NTS and RVLM of WR, around 20% of NAergic vesicles also contained neuropeptide Y (NPY), while in SHR, in NTS over 50% and in RVLM over 60% of NAergic vesicles co-labelled for NPY. In RVLM of SHR co-labelling was found in significantly larger vesicles than in RVLM of WR or NTS of SHR (p<0.001). These results suggest that NAergic vesicles in brainstem areas involved in central cardiovascular control are larger than previous literature reported. Consistent with our earlier data on quantal release, vesicle sizes are increased in the RVLM of SHR. Co-localisation of N/A and NPY in the same vesicles, suggestive of co-transmission, is more pronounced in the RVLM of SHR, again in larger vesicles. Therefore, larger quantal sizes in combination with NPY co-release may be contributing to elevated sympathetic outflow promoting hypertension.