We developed a radioimmunoassay to measure the attack complex of complement (SC5b-9) in serum from patients with systemic lupus erythematosus. The radioimmunoassay used a monoclonal antibody to an antigen of C9, which is absent from native C9 but present on SC5b-9. SC5b-9 was detectable in 13 of 63 normal subjects, with a mean value of 0.5 unit (range, 0 to 4.8), and elevated in 13 of 14 patients with active lupus. Analysis of 108 samples from the patients with lupus revealed a mean value of 10.1 units (range, 0 to 35) when the disease was active and 1.0 unit (range, 0 to 433) when it was clinically stable. SC5b-9 was a more sensitive measure of disease activity than C3, C4, or CH50; its specificity was equivalent to that of C3 and C4. SC5b-9 was elevated in serum from 6 of 49 patients with other forms of glomerulonephritis. Our study documents the presence of SC5b-9 in abnormal serum and correlates its elevation with clinical disease activity in patients with active systemic lupus erythematosus.