OBJECTIVE We studied the effects of large doses of 6-methylprednisolone (6-MP) on serum and cerebrospinal fluid (CSF) soluble CD8 (sCD8) and intercellular adhesion molecule-1 (sICAM-1) levels in clinically active multiple sclerosis (MS) patients. METHODS Paired serum and CSF samples were from 16 patients with definite MS, treated with 6-MP (1 g daily for 6 d) during an active phase of the disease. sCD8 and sICAM-1 levels were determined with ELISA before and after the therapy. RESULTS Before 6-MP treatment, sCD8 levels in CSF were higher in MS patients than in patients with noninflammatory neurological disease and in healthy controls; sICAM-1 levels in serum and in CSF were higher in MS patients than in the two control groups. Ten of the 16 patients showed clinical improvement at the end of the treatment. After the therapy, serum and CSF sCD8 levels increased, whereas serum and CSF sICAM-1 levels decreased. There was no correlation between clinical improvement and laboratory parameters. We evaluated sCD8 and sICAM-1 in serum samples from 10 patients 6 months after the 6-MP treatment, when the disease was clinically silent. Neither sCD8 nor sICAM-1 levels differed from those of the control groups. CONCLUSIONS Our results suggest that high doses of 6-MP can influence serum and CSF sCD8 and sICAM-1 levels in active MS. At least part of the efficacy of corticosteroid treatment in MS might be ascribed to its effect both on the suppressive circuits of immune response, and on the expression of an adhesion molecule that favours lymphocyte trafficking across the blood-brain barrier.