Antigen-antibody complexes in tissues play a central role in the pathogenesis of lupus. Some of the immune complexes are formed in situ, i.e., in the tissues. Others are present in the blood stream, and these circulating immune complexes may deposit in tissues and incite inflammatory mechanisms in those tissues. A variety of techniques are available to measure circulating immune complexes. The assays that have been most studied in SLE include approaches that rely on the interaction of immune complexes with complement proteins, and therefore bind to C1q or contain bound C3. In the process of investigating circulating immune complexes, it was recognized that lupus patients generate serum autoantibodies directed against C1q and other complement proteins. Antibodies reacting with the collagen-like region of C1q are known to be closely linked both clinically and pathophysiologically to lupus nephritis. This chapter describes methods for detection of C1q-binding immune complexes via the C1q solid-phase assay and the related test for autoantibodies to C1q.