We report the results of a prospective study of the complement system in a cohort of 22 multiple myeloma patients: 11 women and 11 men, median age 66 years. There were 10 IgG, 8 IgA, 2 IgM and 2 light chain myeloma patients. Seven were in stage 1, 3 in stage 2 and 12 in stage 3. The serum complement component levels of the three pathways were measured in all patients and compared to normal values of 29 healthy controls. We found a depleted common pathway in 21 patients, and deficient alternative and terminal pathways in 6 patients. There was no difference in the complement profile of myeloma patients in the advanced or early stages of the disease. IgG and IgA myeloma patients had a similar complement profile. Nine patients, 7 with advanced disease, developed 17 infectious episodes. Most of these patients had a deficient classical pathway, but normal alternative and terminal pathways. This profile was not different from the complement system observed in patients without infectious complications. Activation of the three pathways of the complement system was evaluated in all 22 patients. The classical and alternative pathways were activated in most patients in early and late stages, but the terminal pathway (C5-C9) was more frequently activated in the later stages (7 of 12 patients) that in the earlier stages (1 of 10). We conclude that the complement system is deficient in multiple myeloma, most probably because of activation of the system, although no correlation could be demonstrated between the complement system and the clinical manifestations of the disease.