The expression of the CD4 antigen in normal human brain was investigated in parallel by immunohistochemical and Northern blot analyses. With anti-CD4 antibodies detecting different epitopes of the molecule, CD4+ neurons were defined in the cerebellum, thalamus, and pons. CD4+ glial cells were identified in the thalamus and pons. CD4-specific mRNA was detected in all three subareas and in the hippocampus, while other subareas were negative. The CD4+ cells were negative with anti-T cell antibodies (anti-CD2 and anti-CD8), as well as with antimonocyte antibodies (M-M 522 and M-M 42).