negative, that is to say, an increase or decrease, an augmentation or diminution in those factors, acting as vital conditions. Besides the quality there is another highly important factor to be considered in the study of every alteration in the living process, namely, its _amount_. The chemical concentration of the medium, temperature, amount of light, the static and osmotic pressure may undergo more or less variation. The electric stimulus can rise from zero to great intensity and from great intensity can fall to zero. The extent of the alteration determines the intensity of the stimulus. In relation to the intensity, a differentiation of stimulation has been introduced, which is not dependent upon the absolute intensity of the stimulus, that is, upon the extent of the alterations in the external vital conditions, but the intensity of the response that can be observed. One refers frequently to threshold stimulation, to stimulation beneath the threshold, to submaximal, maximal and supermaximal stimulation. Such a classification is in many ways very valuable. It is not only of practical value for the establishment of definite intensities of stimulation, but also for the study of the state of irritability in the living organisms. _The threshold of stimulation_ furnishes roughly a standard for the degree of irritability of a living system. The threshold value of a stimulus is then that degree of intensity which is just sufficient to bring about a perceptible response. The threshold of stimulation is low, that is, the irritability is great, when the intensity of the threshold stimulus is small; the threshold is high, that is, the irritability of a system is small, if the intensity of the threshold stimulus is great. All intensities of stimuli beneath the threshold are sub-threshold stimuli. Here a point must not be overlooked, which in older physiology did not generally meet with sufficient attention. From the fact that the sub-threshold stimuli produce no apparent effects, the wrong deduction must not be made, that they have no effect whatsoever. The conception of the threshold of stimulation originated in the field of muscle physiology and that of the special senses. Here the indicator of the response is, on the one hand, contraction of the muscles, and on the other, conscious sensation. There was a great temptation to consider the stimulus altogether ineffectual, if it produced no conscious sensation or no contraction of the muscle. Today with our finer and more sensitive indicators for the study of the alterations in the living substance, we know in reality that sub-threshold stimuli, which produce no apparent effect in the living substance, can have an effect in reality.