<jats:title>Summary</jats:title><jats:p>Syntaxin‐11 is a member of a family of membrane‐trafficking proteins referred to as soluble <jats:italic>N</jats:italic>‐ethylmaleimide‐sensitive factor attachment protein receptors (SNAREs). Recent studies have shown that syntaxin‐11 is expressed in natural killer cells and cytotoxic T cells and is likely to play a role in the granule exocytosis pathway. However, the biological role of syntaxin‐11 in other immune cells has remained elusive. This study found that stimulation with interferon‐γ upregulated syntaxin‐11 expression in primary monocytes. Experiments using monocytes from patients with familial haemophagocytic lymphohistiocytosis harbouring mutations in the gene encoding syntaxin‐11 (<jats:italic>STX11</jats:italic>), or monocytes from healthy individuals in which syntaxin‐11 was downregulated using specific short‐interfering RNA, demonstrated that syntaxin‐11 was not required for antibody‐dependent cellular cytotoxicity. On the other hand, silencing of syntaxin‐11 expression in primary macrophages enhanced the phagocytosis of apoptotic target cells with a concomitant increase in macrophage secretion of tumour necrosis factor‐α. Moreover, Fcγ‐receptor‐mediated uptake of target cells was also enhanced following silencing of syntaxin‐11 expression in macrophages. In addition, syntaxin‐11 localized to the plasma membrane in macrophages ingesting apoptotic cell corpses. Syntaxin‐11 thus appears to act as a negative regulator of human macrophage engulfment of apoptotic cells and IgG‐opsonized red blood cells.</jats:p>