The effects of cholinergic and adrenergic agonists and antagonists on esophageal bicarbonate secretion in the opossum were studied in vivo using a recirculated unbuffered saline solution and pH stat technique. The basal rate of secretion was 0.28 +/- 0.02 mumol.h-1.cm-2, and this increased in a dose-dependent manner by intravenous administration of carbachol (maximal increase 0.74 +/- 0.07 mumol.h-1.cm-2 at 6 micrograms/kg). Furthermore, like carbachol, the acetylcholinesterase inhibitor edrophonium also increased bicarbonate secretion, whereas atropine and pirenzepine, which had no effect on basal secretion, abolished the increase in secretion produced by carbachol. Intravenous administration of either adrenergic agonists or antagonists had no significant effect on secretion. These data indicate that basal bicarbonate secretion in the opossum esophagus is independent of intrinsic adrenergic or cholinergic activity, and so not under autonomic nervous system control, but that endogenous release of acetylcholine, presumably from parasympathetic nervous fibers, can stimulate bicarbonate secretion through activation of cholinergic M1 receptors.