We have quantified the soluble class I antigen (sHLA) secretion by peripheral blood lymphocytes of 26 multiple sclerosis (MS) patients. Thirteen of them were in a stable phase of the disease, 6 on relapse and 7 suffered from a progressive MS. sHLA secretion was reduced in the presence or absence of phytohemagglutinin in patients with either active or stable MS, being normal after stimulation with a monoclonal antibody anti-CD3. In MS patients, lymphocyte proliferation and immunoglobulin secretion were found to be similar to those of 29 healthy blood donors who comprised the group of controls. These results reflect systemic anomalies in the cell activation process in MS, which seem to be independent of the disease activity. Whether these alterations are specific to MS or are common to other inflammatory CNS diseases remains to be elucidated.