Two patients with systemic lupus erythematosus who developed progressive multifocal leukoencephalopathy (PML) are described. Although the time of PML onset could not be determined with certainty, it probably developed after steroid-induced immunosuppression. However, high-dose corticosteroids appeared to produce transient amelioration in the neurologic disorder. We suggest that PML is an important addition to the list of conditions to be considered in the differential diagnosis when a patient with systemic lupus erythematosus develops neurologic abnormalities.