Within the past 10 years, several investigators have reported the presence of immunoglobulin G in brain neurons. However, because immunoglobulin molecules were only known to be produced by B-lymphocytes, it was suspected that the neurons were taking immunoglobulin G up from the extracellular fluid. The aim of this study was to determine whether immunoglobulin G was actually being produced by the neurons. By immunohistochemistry and Western blotting analysis, we found that immunoglobulin G was also present in adult mouse brain neurons and isolated neonatal mouse neurons, respectively. More importantly, by in situ hybridization, Northern blotting and single cell reverse transcriptase polymerase chain reaction, the transcripts of rearranged immunoglobulin gamma chain and K chain were also found in adult mouse brain neurons. Further, confocal imaging of primary culture neurons showed that immunoglobulin G immunoreactivity was localized in the neuron cytoplasm, axons and dendrites. Immunoglobulin G extracted from the primary culture neurons could also be detected by Western blotting. Furthermore, the results of sulphur-35 or iodine-125 pulse-labeled immunoprecipitation provided additional confirmation that brain neurons could produce immunoglobulin G. Taken together, the results indicated that immunoglobulin G originated from both early generated and adult mouse neurons. Although the bioactivity of neuron-derived immunoglobulin G was not yet clear, we believed that immunoglobulin G might play an important role in neuronal development. (C) 2007 Elsevier Ltd. All rights reserved.