Plasminogen (PGn), which was identified as a secretory product from microglia, increased dopamine uptake and the number of tyrosine-hydroxylase-expressing neurons in cultured rat mesencephalic neurons. 125I-PGn was found to bind specifically much more to mesencephalic neurons compared to other glial cells. The binding was also recognized in plasma membrane prepared from embryonic rat brain. Furthermore, ligand blotting analysis revealed that 125I-PGn binds to a 45-kD protein in plasma membrane. These results suggest that PGn-dependent neurotrophic effects may be induced through the specific binding of PGn to the 45-kD PGn-receptor-like protein in neurons.