The relevance of abnormalities in the distribution of peripheral blood T lymphocyte subsets to the clinical manifestations of multiple sclerosis is not firmly established. A clinical and immunological follow-up of relapsing-remitting multiple sclerosis patients was performed in order to study the relationship of immune changes with the clinical course of the disease. Twenty patients were monitored monthly during a mean time of nine months for peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD19), including the immunoregulatory subsets CD4CD29 (helper-inducer), and CD4CD25) by flow cytometry. A total of 14 untreated relapses was included. The most significant observations were a decrease in T suppressor-inducer CD4+ CD45RA+ subset during clinical relapses (P = 0.028) that was also detectable one month before (P = 0.020) and the lack of changes in CD4+ CD29+ and CD8+ T cells. In addition, variations in the percentage of CD4+ CD25+ activated T helper cells were not associated with clinical exacerbations. These results indicate the existence of a temporal association of immune changes in peripheral blood, but not activation, with the clinical manifestations of multiple sclerosis.