Thirteen patients with severe steroid-resistant or steroid-dependent forms of systemic lupus erythematosus were treated with cyclosporine (average dose 5 mg/kg/d) for an average period of 12 months. In eight patients the disease activity decreased, as substantiated by the reduction in the amount of steroid required to control the clinical manifestations. Interruption of cyclosporine treatment was associated with relapse or worsening of disease in five subjects. These favorable clinical results occurred in the absence of changes in the levels of antinuclear, anti-double-stranded deoxyribonucleic acid autoantibodies or plasma complement components; plasma IgG concentration increased significantly. Six patients had signs of moderate cyclosporine nephrotoxicity that disappeared when the administration of the drug was discontinued. Hypertension was the most serious side effect observed in eight subjects; in every case it was controlled by antihypertensive medicine. These data indicate that cyclosporine may be beneficial in the treatment of some patients with severe forms of systemic lupus erythematosus.