The adrenal medulla is composed principally of groups of adrenergic and nor
adrenergic chromaffin cells, with minor populations of small intensely fluo
rescent cells and ganglionic neurones. Different molecular stimuli evoke di
stinct secretory events in the gland, involving the release of either adren
aline or noradrenaline together with various neuroactive peptides. The natu
re of the secretory response can be controlled at a central level or regula
ted locally within the gland. Specific innervation patterns to the differen
t types of chromaffin cell have been implicated in central regulatory mecha
nisms, while several explanations for regulating secretion locally have bee
n proposed. The differential distribution of various types of receptors bet
ween cell phenotypes, such as muscarinic or nicotinic acetylcholine recepto
rs, histamine receptors, angiotensin receptors and different classes of opi
ate receptors between the two principal chromaffin cell populations could b
e involved in local control. In addition exocytosis parameters could be mod
ulated differently in adrenergic and noradrenergic cells by phenotype-speci
fic mechanisms, possibly involving molecules like Growth Associated Protein
-43, Synaptosomal Associated Protein-25 isoforms or the pll annexin subunit
. The distribution of the various types of calcium channels is also known t
o vary between chromaffin cell subtypes. This short review examines possibl
e ways in which specific innervation patterns in the adrenal gland could be
programmed and discusses exocytosis mechanisms that could differ between c
hromaffin cell phenotypes. Data reviewed here suggest that the adrenal medu
lla should no longer be viewed as a homogeneous entity but as consisting of
an ensemble of individual cell subpopulations each with a distinct secreto
ry response that could in pari reflect its local history.