This series of three papers presents data on a system of neurons, the large supramedullary cells (SMC) of the puffer, Spheroides maculatus, in terms of the physiological properties of the individual cells, of their afferent and efferent connections, and of their interconnections. Some of these findings are verified by available anatomical data, but others suggest structures that must be sought for in the light of the demonstration that these cells are not sensory neurons. Analysis on so broad a scale was made possible by the accessibility of the cells in a compact cluster on the dorsal surface of the spinal cord. Simultaneous recordings were made intracellularly and extracellularly from individual cells or from several, frequently with registration of the afferent or efferent activity as well. The passive and active electrical properties of the SMC are essentially similar to those of other neurons, but various response characteristics have been observed which are related to different excitabilities of different parts of the neuron, and to specific anatomical features. The SMC produce spikes to direct stimuli by intracellular depolarization, or by indirect synaptic excitation from many afferent paths, including tactile stimulation of the skin. Responses that were evoked by intracellular stimulation of a single cell cause an efferent discharge bilaterally in many dorsal roots, but not in the ventral. Sometimes several distinct spikes occurred in the same root, and behaved independently. Thus, a number of axons are efferent from each neuron. They are large unmyelinated fibers which give rise to the elevation of slowest conduction in the compound action potential of the dorsal root. A similar component is absent in the ventral root action potential. Antidromic stimulation of the axons causes small potentials in the cell body, indicating that the antidromic spikes are blocked distantly to the soma, probably in the axon branches. The failure of antidromic invasion is correlated with differences in excitability of the axons and the neurite from which they arise. As recorded in the cell body, the postsynaptic potentials associated with stimulation of afferent fibers in the dorsal roots or cranial nerves are too small to discharge the soma spike. The indirect spike has two components, the first of which is due to the synaptically initiated activity of the neurite and which invades the cell body. The second component is then produced when the soma is fired. The neurite impulse arises at some distance from the cell body and propagates centrifugally as well as centripetally. An indirect stimulus frequently produces repetitive spikes which are observed to occur synchronously in all the cells examined at one time. Each discharge gives rise to a large efferent volley in each of the dorsal roots and cranial nerves examined. The synchronized responses of all the SMC to indirect stimulation occur with slightly different latencies. They are due to a combination of excitation by synaptic bombardment from the afferent pathways and by excitatory interconnections among the SMC. Direct stimulation of a cell may also excite all the others. This spread of activity is facilitated by repetitive direct excitation of the cell as well as by indirect stimulation.