Spontaneous activity of 226 neurons was recorded from in situ mediastinal ganglia in 10 dogs. Forty-two percent of these were active during specific phases of the cardiac cycle, primarily during systole. Cardiovascular-related activity occurred when systolic pressure was between ~70 and 185 mmHg (1 mmHg = 133.3 Pa) whether the pressure was altered by positive inotropic pharmacological agents or cross clamping of the aorta. Twenty percent of the identified neurons displayed respiratory-related activity which occurred during positive pressure inflation or deflation. Thirty-eight percent of the identified neurons displayed bursts of activity or sporadic activity. The activity of 17% of the identified neurons was altered by gentle mechanical distortion of localized regions of the neck, left elbow, ventral thoracic wall, ventral abdominal wall, superior vena cava, right ventricle, or aorta. In the majority of instances cardiovascular- or respiratory-related activity persisted following acute decentralization, indicating that neurons in mediastinal ganglia can function in the absence of influences of central nervous system neurons. Five percent of the identified neurons were activated by single 1–4 ms, 10–20 V stimuli delivered at 0.5 Hz to the nerves connected with either the cranial or the caudal poles of the mediastinal ganglion or the ansae. These neurons were activated after a fixed latency when 0.5 Hz was used and in most instances when 10 Hz was used. These data indicate that 5% or less of the neurons identified projected axons out of the mediastinal ganglia investigated. As the remainder of the neurons identified were not consistently activated after single stimuli delivered individually to the nerves connected directly or indirectly with the mediastinal ganglion, they presumably did not project axons out of the ganglion and thus were considered to be local circuit neurons. Since a number of these local circuit neurons were activated by trains of stimuli delivered to the ipsilateral cardiopulmonary nerves, ansae, rami, sympathetic chain, or cervical vagosympathetic complex, it appears that neural information from a number of sources can modify the behaviour of mediastinal ganglion neurons, substantiating the evidence obtained when various tissues were distorted. Some of the neurons in mediastinal ganglia continued to be activated by trains of stimuli following the administration of hexamethonium, atropine, propranolol, and phentolamine, albeit usually with different latencies of activation. These data support the contention that synaptic mechanisms other than cholinergic and adrenergic ones may exist in mediastinal ganglia, as has been proposed to occur with respect to neurons in the major intrathoracic ganglia. The results of the present experiments indicate that neurons in mediastinal ganglia are involved in cardiovascular and respiratory regulation and that they can be influenced by neural structures in a variety of tissues, some of which are relatively remote from the ganglion. It appears that some of these may be local circuit neurons. Thus neurons in ganglia adjacent to the heart and lungs can behave similarly to neurons located in the middle cervical and stellate ganglia.