The acute-phase proteins, fibronectin (Fn) and serum amyloid P (SAP), are opsonins which by virtue of their adhesive properties may be involved in the glomerular nephritis associated with splenic lupus erythematosus (SLE). Because of their possible involvement in the pathophysiology of lupus, plasma Fn and SAP levels from three strains of autoimmune mice were measured over time to determine if Fn and SAP rose as the mice sickened and renal function degenerated. Baseline levels of Fn and SAP were measured when the mice were between 1.5 and 3 months of age. The characteristic rapid onset of autoimmune disease in MRL/1pr mice was accompanied by a two- to threefold increase in plasma Fn and SAP by Day 100. The B/W mice, which develop autoimmune disease more slowly, did not have a significant increase in plasma Fn and SAP until Day 240. The NZB mice, with the most delayed onset of disease, exhibited a modest but significant elevation of plasma Fn and SAP by Day 360. Histologic examination of the kidneys of B/W and NZB mice indicated that pathological abnormality of the glomeruli and tubules coincided with the elevation of plasma Fn and SAP levels. In contrast, blood samples taken over time from normal BALB/c mice did not possess abnormal levels of Fn or SAP. It appears that elevation of plasma Fn and SAP in the MRL/1 pr, B/W, and NZB mice is related to the onset and severity of autoimmune disease and the subsequent loss of renal function.