A comparison of regulatory cells in spinal fluid and blood in patients with multiple sclerosis and other neurologic diseases. Multiple sclerosis is a disease in which immune abnormalities are present both in the CNS and peripheral blood. Whether these changes are primary or secondary to the disease process is not known. We tested T-cell clones derived from activated lymphocytes in the blood and CSF of MS patients and controls for their capacity to regulate T-cell responses to alloantigens. A wide spectrum of regulatory functions were observed, ranging from marked enhancement to almost complete suppression. Clones from different patient populations and anatomic sites were equivalent in their regulatory functions with the net effect of clones in each compartment being suppression. However, certain clones from CSF and peripheral blood had the capacity to stimulate autologous T cells. Percentages of such clones in the peripheral blood of MS patients were significantly higher than in controls, while percentages in MS and other neurologic diseases (OND) CSF were equivalent. Our data suggest that (1) functional suppressor cells are not lost from the blood or CSF or MS and OND patients, (2) lymphocytes that have entered the CNS in patients with MS and other CNS diseases have equivalent regulatory functions, (3) MS may be an illness in which peripheral immunologic events are important in perpetuating the disease process, and (4) responses to autologous antigens may also play a role in this perpetuation. 