Pulmonary tuberculosis, one of the granulomatous diseases, has few serological markers for its activity. Recently, an increased serum level of vascular endothelial growth factor (VEGF) was detected in patients with Crohn's disease, also a granulomatous disease. We hypothesized that VEGF might be associated with the pathogenesis of pulmonary tuberculosis. We investigated the serum level of VEGF in 43 patients with active pulmonary tuberculosis, 29 patients with old tuberculosis, and 25 patients with acute bronchitis. We were able to examine the serum VEGF levels every 3 mo for a period of 6 mo in seven patients with active pulmonary tuberculosis. We examined the presence of VEGF in the resected lungs of three patients with active pulmonary tuberculosis by immunohistochemistry. The serum levels of VEGF were significantly higher in patients with active pulmonary tuberculosis than in patients with old tuberculosis and acute bronchitis. The decrease in titer of serum VEGF paralleled the clinical improvement of patients with pulmonary tuberculosis. Immunohistochemical staining of the resected lungs demonstrated the presence of VEGF in alveolar macrophages surrounding the lesion. Therefore, VEGF may be associated with the pathogenesis of pulmonary tuberculosis.