We have developed a method for quantitating mannan-binding lectin (MBL)-induced activation of the complement system (MBL-C4-AC) in human plasma. This method and an assay for MBL concentration were applied to plasma samples from healthy individuals and patients with systemic lupus erythematosus (SLE), Crohn's disease (CD) and colorectal cancer (CRC). The MBL concentration was measured by an enzyme-linked immunosorbent assay (ELISA) using monoclonal anti-MBL-antibodies and MBL-C4-AC by an ELISA using solid-phase mannan, incubating with plasma samples and quantitating the complement (C) activation by the use of antibodies against the C split-products C4b/C4c. The MBL concentration was nonsignificantly elevated in plasma from SLE-patients, whereas MBL-C4-AC was suppressed (P < 0.04). There was no correlation between MBL concentration and MBL-C4-AC in plasma from SLE-patients. In contrast, a significant correlation was found between the MBL concentration and MBL-C4-AC in plasma from healthy individuals. The C4 concentration was significantly reduced (P < 0.002) in plasma from the SLE patients and showed a significant correlation to MBL-C4-AC. The MBL-C4-AC assay was highly effective in discriminating the SLE patients from the other patient groups and healthy individuals.