(1) An outline is given of an extended, cooperative investigation now being made on the basis for the physiological activity of onium compounds on the nervous system. (2) Evidence has been obtained which shows that the process is much less simple than is indicated by a number of theories that have been advanced to explain drug action. (3) It would appear that the action of these substances is not due either to their chemical decomposition, their activity as bases or to their distribution coefficients. The mobility of their ions is not, at least, of primary significance. To be physiologically active, these substances must exist in the body fluids as cations. (4) Indirect evidence is given of the necessity of taking into account the probable differences of structure of the mechanism of the nervous system on which these substances act, or (and) the environment at the seat of action. (5) The probability that the first determining factor in the action of these compounds is something in the nature of a selective adsorption depending on the spacial configuration of the groups involved in the ion structure is suggested. The author wishes to express his appreciation to the directors of the Bache Fund of the National Academy of Science for grants made to aid the experimental work of this investigation.