The ganglioside concentration in pooled serum from 20 patients with clinically definite multiple sclerosis (MS) was determined and compared with that in pooled serum from a similar number of healthy blood donors. There as a significant increase in the concentration of ganglioside-bound sialic acid from 691 +/- 57 micrograms/100 ml in the control sera to 926 +/-m 83 micrograms 100 ml in MS patients' sera. The profile of individual gangliosides in the two groups was identical, the four main structures being GM3, GD3, and GD1a and GT1b. The ganglioside pattern and concentration in peripheral blood lymphocytes derived from MS patients and controls was identical with the predominant GM3, and small proportions of Gd3. MS lymphocytes also showed a 39% increase in ganglioside content over control lymphocytes. The implication of such pronounced ganglioside increases is discussed with regard to the impaired immunocompetence of lymphocytes reported in MS.