Using the principles of reaction kinetics we constructed a model for the handling of immune complexes and the pathogenesis of SLE immune complex disease. The model incorporates rate constants for complement- and Fc-mediated clearance, parameters for autoantibody, complement and immune complex levels, and scores for clinical disease activity. The model assumes that complement fixation by immune complexes is a prerequisite for complement-mediated clearance and that disease activity results from immune complex deposition. To test the relationships derived, data from 32 lupus patients were analyzed and the predictions were compared with actual findings. The model predicts a low correlation coefficient between disease activity and immune complex levels (found, r = 0.25, p > 0.1). The model also predicts a poor correlation between disease activity and impaired Fc-mediated clearance in patients with normal complement levels (found, r = 0.10, p > 0.1), but a high correlation coefficient between disease activity and impaired Fc-mediated clearance in patients with hypocomplementemia (found, r = 0.61, p < 0.001). In patients with normal complement levels, the model predicts a good correlation between anti-DNA antibody and immune complex levels (found, r = 0.71, p < 0.001), whereas hypocomplementemic patients should have a good correlation between anti-DNA to CH50 ratios and immune complex levels (found, r = 0.73, p < 0.001). The model predicts that disease activity should correlate better with the product of the anti-DNA to CH50 ratio and the rate constant for Fc-mediated clearance than with any single parameter (found, r = 0.85, p < 0.0001). These significant correlations, which were predicted by the model, suggest that complement-mediated mechanisms are the first line of host defense against immune complex-induced injury, that the efficiency of complement opsonization plays a central role, and that both abnormal complement- and Fc-receptor function leads to active renal disease in SLE.