Induction of steroid metabolism has been reported after rifampicin administration but it is not known how much corticosteroid requirements increase and whether disease control can be satisfactorily maintained with increases in corticosteroid dosage. Because rifampicin may be needed in the treatment of tuberculosis in patients with steroid-dependent asthma, the dose of prednisolone needed to control this condition after rifampicin administration (600 mg daily for 6 wk) was determined in 6 patients in a randomized, double-blind, placebo-controlled trial. The plasma elimination half-life and bioavailability of prednisolone decreased significantly after rifampicin administration, but despite an increase of 93% in the dose of prednisolone (p less than 0.02), asthma control remained inferior compared to placebo. Asthma relapse in a seventh patient necessitated withdrawal from the trial after 2 wk of rifampicin administration despite a five-fold increase in prednisolone dosage. It is concluded that despite substantial increases in the dose of prednisolone the coadministration of rifampicin and prednisolone to steroid-dependent patients may seriously complicate their clinical management.