To investigate the relationship of C1q binding assay (C1qBA) to disease activity in systemic lupus erythematosus (SLE), a retrospective study was carried out on 232 C1qBA performed in 33 patients with SLE. When initial values were assessed (33 tests in 33 patients), there was no relationship between positive and negative C1qBA and abnormal renal function (P = 0.482, Fisher exact test). Of 87 tests performed during active renal disease, 34 (39%) were positive; of 48 tests during active non-renal disease, 25 (52%) were positive; of 83 tests when the disease was inactive, 45 (54%) were positive; and of 14 tests during episodes of infection, 10 (71%) were positive. Corresponding means for the C1qBA were follows: renal 65.66, non-renal 78.02, inactive 56.04, infection 135.79 (no significant differences by Student's t-test). There was no significant relationship with the C1qBA when comparing active disease (renal and non-renal) with inactive disease (chi 2 Yates = 1.875, P = 0.171). When renal function abnormalities were analyzed separately, the C1qBA values were independent of azotemia or proteinuria (chi 2 Yates = 1.399, P = 0.237). Patients were seen with progressive renal disease who had consistently negative C1qBA, as well as patients with benign clinical courses despite elevated C1qBA. The discordance of the C1qBA results with disease activity in SLE highlights the limitations of immune complex (IC) determinations by a single technique, and stresses the importance of evaluating such tests in terms of both their specificity and sensitivity. These data further suggest that the relationship of IC to the disease process in SLE may be a complex one.