Background: Production of SIgA or SIgM for therapeutic application remains an unsolved issue. Results: Human plasma-derived polyclonal, polymeric IgA and IgM associate with recombinant or colostrum-derived human secretory component to form digestion-resistant, functionally active SIgA-and SIgM-like molecules. Conclusion: SIgA and SIgM can be rebuilt ex vivo from plasma-derived IgA/IgM. Significance: This would enable development of SIgA/SIgM-based mucosal therapeutics.