If it is true that all primary effects of stimulation consist either in an excitation or depression of the metabolism, and that all other effects of stimulation secondarily follow this primary alteration of the metabolism of rest, then every thorough analysis of the mechanics of reaction must have its beginning in the investigation of these primary processes. I desire to adopt this method here and will analyze somewhat further the _primary process of excitation_ and its immediate and remote sequences. This will be followed later by the analysis of the process of primary depression and its results. The investigation of the more obscure processes in the living substance places us in a difficult position, for their details cannot be observed by the unaided senses. That which we can perceive is merely the grosser vital action, consisting of a complex combination of the individual processes, the total result of a multitude of different components. For this reason the conception of excitation can only be established by observations based upon the combined vital actions, which are produced by the effect of stimulation upon the complex system. In the beginning, the process of excitation was studied exclusively on the muscle and nervous system. A physical factor served as indicator, such as muscle contraction or production of electricity. These showed, besides the direct and primary effect of stimulation, the secondary process of conductivity. Even graphic registration is merely an expression of the phenomena composed of a great mass of individual elements. The visible course of the phenomena, as shown, for instance, by the latent period by the ascent and descent of the curve of contraction, represents as it were a reflected picture of the actual excitation processes similar to an object seen in a distorting mirror; the first and the last parts of the process are not even perceptible. Later, when organ physiology was extended into a cell physiology the processes of excitation were studied in numerous simple organisms, such as the plant cell, the rhizopoda, the infusoria, etc. Later, in this way, by the use of comparative methods many essential facts were discovered. However, even the single cell, in spite of its minuteness, is, compared with the size of a molecule, a gigantic system, and it would be a grave error if we should consider this system even in its simplest aspect as homogeneous. In order, therefore, to analyze the vital activities in the cell, cell physiology must endeavor to penetrate into molecular conditions. For this purpose the indicators employed must be essentially of a chemical nature, capable of magnifying the processes of molecular dimension to such a degree that we are enabled to base conclusions upon these not otherwise directly perceptible phenomena. To obtain a sufficient magnification we must necessarily place somewhat larger quantities of living substance under observation and apply a stimulus of such frequency or length