The neurogenic potential of the postnatal neocortex has not been tested previously with a combination of both retroviral and bromodeoxyuridine (BrdU) labeling. Here we report that injections of enhanced green fluorescent protein (eGFP) retrovirus into 134 postnatal rats resulted in GFP labeling of 642 pyramidal neurons in neocortex. GFP-labeled neocortical pyramidal neurons, however, unlike GFP-labeled glia, did not incorporate BrdU. Closer inspection of retrovirally labeled neurons revealed microglia fused to the apical dendrites of labeled pyramidal neurons. Retroviral infection of mixed cultures of cortical neurons and glia confirmed the presence of specific neuronal-microglial fusions. Microglia did not fuse to other glial cell types, and cultures not treated with retrovirus lacked microglial-neuronal fusion. Furthermore, activation of microglia by lipopolysaccharide greatly increased the virally induced fusion of microglia to neurons in culture. These results indicate a novel form of specific cell fusion between neuronal dendrites and microglia and further illustrate the need for caution when interpreting evidence for neuronogenesis in the postnatal brain.