Background: Parthenium hysterophorus is the commonest cause of airborne contact dermatitis in India. Azathioprine has been shown to be effective and safe in parthenium dermatitis, but there are no reports of comparison of steroids and azathioprine in this condition., Aims: To study the therapeutic efficacy of azathioprine versus betamethasone in patients having contact dermatitis to parthenium and compare the side effects of the drugs., Methods: Fifty-five patients of airborne contact dermatitis to parthenium were randomly assigned to treatment with azathioprine 100 mg daily (group A) or betamethasone 2 mg daily (group B), for 6 months in a blinded manner. The patients were evaluated every month for 6 months to determine the response to treatment and side effects and then further followed up for another 6 months to determine any relapse., Results: There were 26 patients in group A and 29 in group B, of which 20 patients of group A and 21 of group B completed the study. Nineteen (95%) patients in group A and all 21 (100%) patients in group B had an excellent response (complete remission) to treatment (P=0.0156 vs. 0.0005). The patients in group B, however, had more adverse effects (Fisher exact, P