A simple and reproducible method for the measurement of serum neutrophil clustering activity was developed. High clustering activity was found in 19/30 patients with active systemic lupus erythematosus (SLE), and 14/20 of those with severe disease flares. In contrast, 0/10 patients with quiescent SLE and 2/20 patients with rheumatoid arthritis had high neutrophil clustering activity. Particularly high clustering activity was found in patients with SLE with lupus glomerulonephritis and in certain patients with central nervous system disease. An inverse correlation was found between neutrophil clustering activity and peripheral blood neutrophil count in patients with SLE not treated with glucocorticoids, and clustering activity was high in all patients with low neutrophil counts in this group. A moderate correlation was found between neutrophil clustering activity and C1q binding circulating immune complexes. Non-steroidal anti-inflammatory drugs and glucocorticoids had little direct effect on neutrophil clustering activity.