Rifampicin therapy caused exacerbation of skin lesions, rising serum pemphigus antibody titres, and decreased serum betamethasone levels in a 59-year-old man with pemphigus vulgaris. Exacerbation of pemphigus was confined to the period of rifampicin therapy and seems to be best explained by the effect of rifampicin on the metabolism of betamethasone. Physicians prescribing rifampicin for the treatment of tuberculosis should be aware of its potential to produce such an important adverse reaction.