A brief investigation was made of various organic and inorganic solvents for the dissolution of urinary calculi in vitro and Albright’s (1) citric acid buffer and a solvent designated in this investigation simply as “G” (33) were shown to be the most efficient solvents. Further investigation showed that something was necessary to increase the efficiency of these solvents, as the dissolution would proceed to a certain point where the solvent ceased to act. It was at this point that the investigation changed its course and the attack was centered on the organic colloidal matrix in the structure of the stone. It is a well known fact that this organic matrix is resistant to weak acids and bases (30) and therefore the course of the investigation pointed to those most remarkable agents, “the enzymes”, which due to their enormous amount of surface energy are capable of producing astonishing results. The enzymes investigated were not selected for their specific action, but they were selected for the purpose of studying the effect of their surface energy on the colloidal matrix of urinary calculi. The investigation indicates that a calculus pretreated with urease for fifteen minutes, followed by a 6 hour irrigation with “G” (33) solution is sufficient to cause dissolution and disintegration in nearly all of the one hundred calculi selected at random. (See Table 5) The ability of urease to hasten disintegration may be due to its activity on the colloidal matrix, causing it to swell, thereby giving back the former hydrotropic properties mentioned by Snapper (52). Colloidal material was isolated from a large calculus and was subjected to the action of urease. After 6 hours the colloids from the calculus had swollen approximately five hundred times their original volume, and changed from a dark brown-colored material to a white translucent gel. These organic colloidal matrices of urinary calculi are apparently of a reversible nature and irreversible as investigators have assumed in the past (30). Investigations were made and reported in various sections of this paper on the ability of other enzymes, peroxide, and acids to act as dissolution agents or as aids to dissolution. An efficient in vitro irrigator Fig. 1 is described and its merit in the irrigation of urinary calculi lies in the facts that its construction is simple, its rate of flow can be accurately regulated by a slight manipulation, and the calculus can be treated in various ways without removing it from the original crucible. It now remains for the urologist to investigate the possibility of in vitro dissolution, using the above auxiliary agent. It is suggested that the urease might be used simultaneously with the irrigation solvent. / Ph. D.