Total lymphocyte counts and T and SIg+ cell numbers in peripheral blood were determined in 74 healthy controls and 44 MS patients. Twenty-five patients were studied in relapse and at two intervals after ACTH. Nineteen had not relapsed for 6 months but most had progressed clinically. MS patients showed significantly lower total lymphocyte counts which were not correlated with disease activity. Subpopulation analyses showed the MS patients to have significantly lower T cell numbers and significantly elevated SIg+ cell numbers and percentages. Although T cell numbers were low in all phases, both T and SIg+ cell abnormalities were maximal in progressive disease or in the recovery phase after relapse and a significant fall in T cell percentage and rise in SIg+ cell number was confirmed in serial studies of 16 patients followed from relapse to recovery. SIg+ cell numbers correlated negatively with relapse rate and correlated positively with the ratio of disability to number of relapses. The incidence in MS patients of HLA A3 was significantly increased and of HLA B12 and HLA BW40 significantly decreased but no correlation was seen between HLA phenotype and T, SIg+ or total lymphocyte counts. It is suggested that the peripheral blood SIg+ cell abnormalities and some of the T cell abnormalities are secondary to the pathological process, perhaps due to antigenic stimulation and particularly in non-relapsing progressive disease. Their possible role in influencing recovery or progression is discussed.