Numbers of B cells spontaneously secreting Ig (IgG, IgA, and IgM) were determined by a plaque-forming cell (PFC) assay simultaneously in the peripheral blood and bone marrow of normal individuals, patients with systemic lupus erythematosus (SLE), and patients with primary Sjögren's syndrome. Normal individuals had 382 (+/- 89) PFC per 10(6) mononuclear cells in peripheral blood. Patients with either active or inactive Sjögren's syndrome had normal numbers of spontaneous Ig-secreting cells in peripheral blood (P greater than 0.2). Conversely, patients with inactive as well as active SLE had markedly increased spontaneous PFC (P less than 0.05 and P less than 0.001, respectively). Patients with active SLE had significantly greater PFC than patients with inactive SLE; 3,984 (+/- 960) versus 1,605 (+/- 527) PFC per 10(6) mononuclear cells (P less than 0.05). The lack of increased numbers of activated B cells in the blood of patients with Sjögren's syndrome was not explained by a preferential sequestration of activated B cells in the bone marrow. However, of particular interest was the finding that the bone marrow served not only as a major source of virgin B cells but as a lymphoid organ of either in situ activation of B cells or sequestration for activated B cells. Normal individuals had approximately a 20-fold relative increase of activated B cells per 10(6) mononuclear cells in the bone marrow compared to peripheral blood, while patients with inactive and active SLE both had a 35-fold relative increase in activated B cells in bone marrow compared to peripheral blood. The potential relevance of circulating activated B cells and their sequestration in lymphoid organs is discussed concerning the discrepancy in this regard between Sjögren's syndrome and SLE, and our understanding of the significance of polyclonal B cell activation in the pathogenesis of these diseases.