The enterochromaffin-like (ECL) cells, which are the predominant endoc
rine cell type in the acid-producing part of the vertebrate stomach, a
re characterized by numerous, electron-lucent vesicles and few electro
n-dense granules in the cytoplasm. The biological and physiological si
gnificance of the ECL cells remains poorly understood. They produce an
d store histamine and pancreastatin and are thought to produce an as y
et unidentified peptide hormone. The most important clue to their func
tion is their willingness to respond to changes in circulating gastrin
. The present review presents current knowledge of the biology and phy
siology of the rat stomach ECL cells. Examination of serially sectione
d ECL cells has revealed that the cytoplasmic vesicles almost invariab
ly contain an electron-dense core, suggesting that perhaps the distinc
tion between granules and vesicles is artificial. We propose a life cy
cle of the secretory organelles in the ECL cells with a progressive de
velopment from granules to vesicles. The results showed that the gastr
in-evoked release of histamine and pancreastatin was accompanied by lo
ss of vesicles, and that synthesis of histamine and pancreastatin was
accelerated by sustained infusion of gastrin, a treatment that was ass
ociated with renewal of vesicles. The events described are instrumenta
l in bringing about a change in the ''steady state'' or ''equilibrium'
' of the ECL cells, from a non-stimulated, resting state to a gastrin-
stimulated, active state. This change is attained within six to eight
hr. The next ''steady state'' change is that from ''normal-sized'' but
active ECL cells to ''hypertrophic'' ECL cells. The increase in cell
size is complete after about one week. The gastrin-evoked increase in
the ECL cell self-replication rate is maximal after about 10 days, aft
er which time there is a gradual return back to pre-stimulation values
. The ECL cell density increases fairly slowly and does not reach maxi
mum (four-fold increase) until after 20 weeks of hypergastrinemia. The
activity of the histamine-forming enzyme, histidine decarboxylase, is
elevated by gastrin and remains elevated for as long as the gastrin s
timulus is maintained (the longest time studied was 20 weeks). The phy
siological significance of the ECL cells is probably related to their
capacity to produce and store histamine and an as yet unidentified pep
tide hormone. The ECL cells are thought to be the source of histamine
necessary for the gastrin-evoked acid response. In addition, prelimina
ry evidence suggests that the ECL cells and the anticipated ECL cell h
ormone play a role in bone formation.