Cold injury of both the dry and the moist types are of the utmost importance in military operations, and are likely to assume even greater importance in the event of polar warfare. The modern literature on frostbite began with Napoleon's retreat from Moscow in 1812 when his surgeon, Baron Larrey recorded the disastrous event in his memoirs. Since then it has been the various wars of the western world that has provided the main stimulus for investigation into the cold problem. The experimental investigation has effected little positive benefit by way of management of an acute cold injury, but it has served to break down many time honoured doctrines, especially the theory that slow thawing of a frozen limb provided the best treatment. The significance of the various events that occur in the tissues during a freezing reaction are not agreed on by all workers, but the course of the reaction and especially the danger of the secondary effects during thawing are well known. The present investigation concerned an attempt to observe microscopically the vascular changes in the rat mesoappendix according to a technique of Zweifach. A cold point apparatus described by Hass and Taylor was utilized for exact freezing of a capillary bed. The influence of ten selected drugs on the reactions of the vascular bed after freezing was tested alternately with control rats. Procaine, priscoline, benadryl, etamon, hydergine, apresoline, chlor-tripolon, rutin, ascorbic acid, and histamine were tested. The criteria for a drug effect included delay in onset of vascular stasis, lessening the rate and extent of the stasis, and resumption of circulation in static vessels. No significant difference was observed between the treated and the control animals. In an effort to confirm this impression grossly, the hind legs of rats were frozen in a carbon dioxide and ether mixture at -20°C. for twenty seconds. The changes observed grossly following thawing were described numerically and the arbitrary concept of an Injury Index was utilized which could be expressed graphically on a day by day basis. Of the same ten drugs tested, procaine, priscoline, benadryl, etarnon, hydergine, and ascorbic acid were found to have no significant effect. Chlor-Tripolon and histamine were found to have an adverse effect, and apresoline, and especially rutin, were found to have a probably significant beneficial effect. The value of rapid thawing in water at 42°C. was consistently confirmed throughout all gross experiments. / Medicine, Faculty of / Graduate