Warts, hypogammaglobulinaemia, infections, myelokathexis (WHIM) syndrome is an inherited immune disorder associated with CXCR4 gene mutations. Recent studies suggested that impaired receptor downregulation and enhanced chemotactic responsiveness to stromal‐derived factor‐1 (SDF‐1), the sole cognate ligand for CXCR4, may account for the characteristic features of WHIM patients. This study evaluated whether the interaction of SDF‐1 with CXCR4 could block constitutive apoptosis of peripheral blood neutrophils from congenital neutropenia patients and controls. SDF‐1 was found to be a potent anti‐apoptotic factor for WHIM neutrophils harbouring a truncating CXCR4 mutation, but not for neutrophils from control individuals, thus supporting the notion that such mutations may confer enhanced functional responses.