In vertebrates vagal preganglionic neurons are found in two principle locations in the brain-stem, the dorsal vagal motor nucleus and areas lateral to the dorsal vagal motor nucleus centered on the nucleus ambiguus. In elasmobranch fish 8% of vagal preganglionic neurons are located outside the dorsal vagal motor nucleus; these are all cardiac vagal motoneurones. This proportion increases from fish through amphibians to mammals in which over 30% of vagal preganglionic neurons are outside the dorsal vagal motor nucleus; in the cat 80% of cardiac vagal motoneurons are in the nucleus ambiguus. Vagal tone is the major determinant of heart rate and its relationships to environmental factors (e.g. temperature, hypoxia). Activity in subpopulations of cardiac vagal motoneurons varies with the respiratory rhythm in fish and mammals due to central interactions between respiratory and cardiac vagal motoneurons. This generates cardio-respiratory synchrony in dogfish and respiratory sinus arrhythmia in mammals. The appropriate central connections are established during development. In the neotenous axolotl all vagal preganglionic neurons are in the dorsal vagal motor nucleus; 15% are lateral to the dorsal vagal motor nucleus following metamorphosis, induced by injection of thyroid hormones; a change which may relate in part to the switch from gill to lung-breathing. Respiratory sinus arrhythmia first appears at around normal term gestation in the premature human neonate, at a time when they would normally be switching from reliance on the placenta to lung-breathing.