The purpose of this study was to investigate the cellular source and significance of vascular endothelial growth factor (VEGF) which, as reported previously, is elevated in the sera of pulmonary tuberculous patients. We obtained peripheral blood mononuclear cells (PBMCs) from 28 patients with active pulmonary tuberculosis, from 11 healthy controls who were positive for purified protein derivative of tuberculin (PPD), and from eight healthy individuals who were negative for PPD. We incubated the PBMCs with PPD in the presence or absence of major histocompatibility (MHC) class I or class II antibody in vitro, and measured the VEGF levels of culture supernatants. We also analysed the source of cells that secrete VEGF by using flow cytometry with intracellular staining. The T lymphocytes of active tuberculous patients secreted a higher level of VEGF than those of healthy controls. This production of VEGF was inhibited by adding MHC class II antibody. The addition of MHC class I antibody, however, did not inhibit. We propose that CD4+ T lymphocytes are almost certainly the cells that produce VEGF in response to PPD. VEGF production might be associated with an antigen-specific immune reaction via CD4+ T lymphocytes in tuberculosis.