SummaryWe have shown that corticosteroids and non‐steroid anti‐inflammatory agents suppress the increase in skin thickness in response to irritants applied to guinea pig skin. The combination of salicylic acid with corticosteroids and acetyl salicylic acid with hydrocortisone results in an antagonistic reduction of their anti‐inflammatory activities. Indomethacin, in contrast, acts synergistically with corticosteroids.Sodium salicylate also suppresses DNA synthesis of human skin in vitro and hydrocortisone sodium succinate is able to abolish this suppression. This result, together with the results of trials on human volunteers, suggests that our findings may be relevant to the use of preparations containing combinations of non‐steroid and steroid anti‐inflammatory drugs in the clinical situation.The antagonism between salicylates on the one hand and indomethacin and steroids on the other, has been demonstrated by our work on the skin of man and the guinea pigs. A similar effect had been previously described in adjuvant induced arthropathy in the rat. These findings should alert clinicians who use anti‐inflammatory agents in various combinations, to the possible reduction of clinical effect due to antagonism between salicylates and other anti‐inflammatory drugs.