Z39Ig is a recently-identified gene with immunoglobulin-like domains whose function is unknown. We examined expression of Z39Ig in 1432 human cDNA libraries, and found it primarily in synovium of patients with rheumatoid arthritis, in placenta, and in lung. We analyzed its co-expression pattern using the Guilt-by-Association (GBA) algorithm, and found that it is most similar in expression to early genes in the classical complement system (C1qA, C1qB, C1qC, C1r, and C1 inhibitor), MHC class II genes (HLA-DR alpha, HLA-DR beta 1, and HLA-DP alpha 1), Fc receptors (Fc gamma RIIa and Fc epsilon R1), lysosomal protein (LAPTm5), tissue transglutaminase, and macrophage receptors (MARCO and CD163/M130). The sequence and expression data suggest that Z39Ig is a cell surface receptor, expressed in activated macrophages, and linked with the classical complement system, most likely in phagocytosis preceding antigen presentation. Knowledge of this gene may contribute to better understanding of the role of complement and activated macrophages in rheumatoid arthritis and systemic lupus.