The immune response to pathogens or injury relies on the concerted release of cytokinesand proteins with biological activity important for host protection, host defense, and woundhealing. Consequently, the secretome of immune cells provides a promising resource fordiscovery of specific molecular markers and targets for pharmacological intervention. Here,we employ label-free MS for unbiased, quantitative profiling of the human monocytic cellsecretome under different proinflammatory stimuli. The quantitative secretome profiles revealthe highly stimulus-dependent cellular response and differential, specific secretion of morethan 200 proteins, including important proinflammatory proteins and cytokines.