O ral high-dose methylprednisolone treatment is efficacious in acute optic neuritis (O N) and attacks of multiple sclerosis (MS). The responses to treatment in subgroups of patients participating in two randomized, controlled trials were assessed. Fifty-eight patients with O N and 51 patients with attacks of MS were treated with placebo or oral methylprednisolone (500 mg daily for five days with a 10-day tapering period). A gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan was obtained at baseline in 66 patients, and 29 patients underwent repeated MRI studies. Seventy-four patients underwent lumbar puncture before treatment. The odds ratio (O R) of improvement after methylprednisolone treatment (a one point change in the visual function system score of the Kurtzke Expanded Disability Status Scale (EDSS) in O N or in the EDSS score in attacks of MS) was higher in patients with enhancing lesions on baseline MRI (one week: O R 15, P-0.02; eight weeks: O R 4.6, P-0.02). Methylprednisolone treatment suppressed G d-enhancement after one week (P-0.001) and three weeks (P-0.001). C erebrospinal fluid measures of intrathecal inflammation correlated with the area of G d-enhancement but did not correlate as closely with the treatment response as did the results of G d-enhanced MRI. These findings suggest that the resolution of intrathecal inflammation as assessed by G d-enhanced MRI is a major effect of oral high-dose methylprednisolone.