The use of measurement of skin thickness in guinea pigs has been compared with other techniques for assessment of topical applications. This method has provided us with an accurate evaluation of the corticosteroid dose-response curve and the effect of bases. The method has shown that non-steroid prostaglandin synthesis inhibitors can also be demonstrated to possess topical anti-inflammatory activity. As expected, indomethacin acts synergistically when formulated with hydrocortisone. Contrary to our expectation, both salicylic acid and acetylsalicylic acid show antagonism with hydrocortisone. This finding may be of clinical significance. We have also found that a combination of salicylic acid and indomethacin produces striking inflammatory changes in guinea pig skin which points to interaction of these two drugs in the guinea pig. The relevance of this phenomenon to both the mode of action of the two drugs and their use in clinical practice remains to be elucidated, but preliminary tests suggest that similar changes take place in human skin.