Opiates modulate many macrophage functions. Microglia, the resident macrophages of the brain, migrate to sites of inflammation within the CNS. Using primer sets designed to span the entire open reading frame of the human brain mu opioid receptor (MOR), we found that microglial cells constitutively expressed MOR mRNA. The cDNA sequences of the MOR open reading frame in microglia were identical to those of human brain tissue. Using enriched human fetal microglial cell cultures, we found that morphine potently inhibited the directed migration (chemotaxis) of microglial cells toward C5a in a dose-dependent manner with an IC50 value of 1 fM morphine. We also found that DAMGO, a selective MOR ligand, dose-dependently suppressed microglial cell chemotaxis with an IC50 value of 1 nM, which was significantly attenuated by 10 nM beta-funaltrexamine. Taken together, these findings suggest that activation of constitutively expressed MOR inhibits microglial cell chemotaxis and support the notion of an anti-inflammatory role of MOR within the brain.