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Urinary sialic acid-containing trisaccharides, total sialic acid, and serum sialic acid were studied in 17 patients with systemic lupus erythematosus (SLE) and in 15 healthy controls. The urinary excretion of sialyllactose, measured by a gas chromatographic method, was significantly greater in patients with SLE (37.4 +/- 21.4 mg/24 hours, SD) than in the control subjects (13.7 +/- 3.8 mg/24 hours, p less than 0.001). The mean excretion of sialyl-N-acetyllactosamine (16.6 +/- 8.5 mg/24 hours) and total sialic acid (82.5 +/- 29.4 mg/24 hours) was also greater in the SLE group than in the controls (8.7 +/- 2.8 and 58.0 +/- 16.0 mg/24 hours, respectively; p less than 0.01). Serum levels of sialic acid were correspondingly higher in the SLE patients (84.4 +/- 20.4 mg/100 ml) than in the controls (63.7 +/- 6.5 mg/100 ml, p less than 0.001). Urinary excretion of sialyl-lactose correlated positively with clinical disease activity (p less than 0.001) and with anti-DNA antibody levels (p less than 0.05). On the average, patients with moderate or severe disease excreted three times more sialyl-lactose than did those with mild or inactive disease. Our results suggest that the excretion of sialyl-oligosaccharides reflects disease activity in SLE.