Six patients with histologically proven HBsAg-negative chronic active hepatitis (CAH), who were initially treated successfully with prednisolone with or without azathioprine, developed unacceptable adverse effects due to prednisolone. In all six patients the liver disease relapsed on reduction of the prednisolone dose and they subsequently entered a trial of low dose D-penicillamine. Two of the patients required early withdrawal of D-penicillamine and a third patient, who had a good clinical and biochemical response initially, developed heavy proteinuria at 14 months. In the remainder, D-penicillamine was well tolerated and the liver disease satisfactorily controlled permitting reduction of the prednisolone dose to 2.5 mg daily. We conclude that in this subgroup of patients with HBsAg-negative CAH and major prednisolone-induced adverse effects, D-penicillamine is an effective alternative therapy although side effects are common.