Six patients with early, mild, relapsing-remitting multiple sclerosis were studied with monthly gadolinium-enhanced magnetic resonance imaging scans for 8 to 11 months. Numerous enhancing lesions were observed irrespective of clinical activity. Four of the 6 patients had one or more enhancing lesions present on each examination. The other 2 patients had enhancing lesions noted in 7 and 9 of 11 months. In contrast, only two clinical exacerbations were observed during the study period. Neither the exacerbations nor other changes in symptoms or signs correlated with occurrence of the enhancing lesions. Enhancement generally persisted for less than 1 month. The opening of the blood-brain barrier as reflected by gadolinium enhancement on magnetic resonance imaging may represent ongoing disease activity in patients with mild, relapsing-remitting multiple sclerosis who are clinically stable. The frequency of these lesions appears to be sufficient to use as an outcome measure in clinical trials testing clinical efficacy in patients with early, relapsing-remitting multiple sclerosis.