The aim of this study was to evaluate the frequency and intensity of cerebral atrophy using CT scanning and the possible relation to corticosteroid therapy or disease in systemic lupus erythematosus (SLE) and to analyse the relationships between cerebral atrophy and activity disease and neuropsychiatric manifestations in lupus patients. We studied 107 consecutive SLE patients (American Rheumatology Association 1982 criteria) who were taking steroid drugs at the time and not selected for any particular manifestation (group 1). A complete clinical, neurological and laboratory evaluation was performed. The American College of Rheumatology's classification for neuropsychiatric manifestations and SLE disease activity index for activity were employed. Group 2 comprised 39 non-SLE patients with oral chronic steroid use (1 mg/k/day for more than 3 consecutive months); 50 normal individuals were the controls (group 3). There were no demographic differences between the groups. Brain CT was performed in all individuals and the frequency and the intensity (minimal, moderate and severe) of atrophy analysed, through well-defined measures and indices, by two neuroradiologists. Cerebral atrophy was significantly more frequent in groups 1 and 2 than in group 3, but with no significant difference between groups 1 and 2. The severity of cerebral atrophy was significantly higher in SLE patients (p<0.05), independent of steroid dose or duration of disease. In both groups no patient presented severe atrophy. Lupus patients with and without cerebral atrophy presented neuropsychiatric manifestations and activity disease in a similar proportion. The more frequent neuropsychiatric manifestation in lupus patients with cerebral atrophy was seizures (p<0.05). Chronic glucocorticoid therapy was responsible for cerebral atrophy, with a comparable incidence in both lupus and non-lupus patients compared to age and gender-matched normal subjects untreated with glucocorticoids. The disease activity was not related to cerebral atrophy in group 1 and seizures were the neurologic manifestation related to cerebral atrophy. The severity of the cerebral atrophy was independent of steroid dose, or duration of treatment. Moreover, the disease itself contributes to the severity of this process, but not to the development of cerebral atrophy.