Therapeutic use of cutaneously applied DMSO demands thorough knowledge of resorption, distribution, storage, elimination, and metabolic pathways in man and animals. Sand 3H-labeled DMSO was used to elucidate these factors. Our results cover the unchanged DMSO as well as its metabolite, DMS02, which was described by Gerhards and Gibian. Unless indicated otherwise, DMSO as a 9OT solution was used for the experiments. If DMSO is applied cutaneously, the rapidity of its appearance in blood, and the course of its concentration in blood, supplies information about duration and speed of resorption via the skin. FIGURE 1 shows curves indicating the course of radioactivity in an arteriovenous shunt in the rat. After cutaneous application, impulses measured in flowing blood increased rapidly. Ten minutes later the maximum count was registered. At this time, concentration in blood was about 18 mg'i'. The half-time of DMSO in blood was greater than 10 hours. Following intravenous injection, the number of impulses fell t o half the initial value after a few minutes, and remained a t the same level for 6 hours. The course of radioactivity in an arteriovenous shunt in awake beagle dogs is similar to that in rats. After cutaneous application the impulse rate in blood increased slowly, a t first, and after 45 minutes reached a plateau, which remained almost unchanged for 7 hours. Concentration in blood varied between 8 and 12 mg'?. In man, radioactivity in blood could be registered even in the first sample, which was drawn as soon as 5 minutes after cutaneous application. A maximal plateau was recorded between the 4th and the 6th hours. This plateau remained almost unchanged for 1: to 3 days. In order to be able to determine quantitatively the amount of cutaneous resorption, we studied, a t different time intervals after application, the amount of activity located in the dermis. In beagles, DMSO was applied once only, and after 1, 4, 7, and 14 days the treated skin regions were excised. These experiments showed that, in the dog, after 4 hours about 80% and after 24 hours more than 90% of the cutaneously applied dose penetrate the skin barrier. There was an almost linear decline of radioactivity in the dermis for 2 weeks. On day 14,0.03% of the applied dose could be registered. 35