Perivascular and meningeal macrophages are important for immune surveillance in the healthy and the injured brain. Monocyte chemoattractant protein-1 (MCP-1) regulates macrophage migration and permeability of the blood brain barrier. In the present study, we investigated the influence of MCP-1 or/and chemokine receptor 2 (CCR2)-deficiency on macrophage turnover. The results showed no influence of single MCP-1- or CCR-2-deficiency, but double-deficient mice revealed a virtual absence of blood-borne macrophage recruitment. This finding emphasizes that the MCP-1/CCR2 axis is crucially important for macrophage turnover and compensatory mechanisms remain only partially sufficient to sustain regulatory functions.