Proteinase levels are increased in multiple sclerosis (MS) lesions and are implicated in demyelination. The cellular origins of the activity are not known, but inflammatory cells of hematogenous origin are one possibility. We studied the levels of two lysosomal proteinases implicated in the proteolysis of myelin basic protein, cathepsin B (CB) and cathepsin D (CD), in peripheral blood mononuclear cells (PBMCs) of 20 stable relapsing-remitting MS patients. We prepared and assayed cell lysates of PBMCs from the MS patients, 10 patients with other neurologic diseases (OND), and 12 normal controls (NC). Mean CB activity expressed as milliunits of activity per million cells was significantly increased in MS patients (7.86 +/- 0.54) compared with OND (6.80 +/- 0.74) and NC (5.94 +/- 0.28) cells (p < 0.05). CD levels were not significantly increased. To determine whether the increase was generalized or limited to a subset of cells, PBMCs were fractionated by plate adherence. CB levels in the adherent fraction (AD) of the 20 MS patients were higher than in the nonadherent fraction (NA), and the AD:NA ratio of CB in MS was higher than that in controls. This would be consistent with an increase in CB levels in monocytes and macrophages, cells known to be activated in the peripheral blood of MS patients and implicated as effectors of demyelination.