The interaction between chemokines and their recepto rs leads to selective recruitment of cells to foci of inflammation. C ross-sectional studies have reported significantly different expression of chemokine recepto rs C XC R3, C C R5 and C C R2 on peripheral blood lymphocytes in multiple sclerosis (MS) compared with controls. C ells expressing these receptors are likely to play a pathogenic role as suggested by studies of experimental autoimmune encephalo myelitis. A lso, immunogenetic studies of nonfunctional C C R5 recepto rs in MS patients, due to 32d deletion, demonstrated a delay in time to next relapse. The aims of this study were to detect any changes in the serial expression of chemokine recepto rs C C R2, C C R3, C C R5 and C XCR3 on peripheral blood C D4 lymphocytes from patients with MS and to correlate the changes with relapses. Upregulation of C XCR3 expression on peripheral blood C D4 lymphocytes was associated with all relapses and C C R5 expression was significantly affected with all relapses. C linical recovery, with or without intravenous methylprednisolone treatment, coincided with the return of C XC R3 towards baseline in all but one case. Fluctuation in the expression of C XC R3 and C C R5 was also significantly greater in clinically stable patients with MS compared with controls, which may be due to subclinical disease activity. These findings provide further support for the view that C XC R3 and C C R5 antagonists could have a therapeutic value in MS.