We studied the kinetic alterations of angiotensin-II (A-II) and nitric oxide (NO) in radiation pulmonary fibrosis (RPF) to determine the roles of these two types of vasoactive substances in the pathogenesis of RPF. We irradiated the right hemithorax of male Wistar rats with single doses of 0, 15, and 30 Gy of 60Co gamma rays and we examined the lung parenchyma at 1, 3, 5, and 7 months following the radiation. The rats were killed at the stated intervals and samples were obtained from the right lung. We measured types I and III procollagen mRNA by in situ hybridization and demonstrated the synthesis and distribution of A-II in the pulmonary tissue by immunohistochemistry. The formation and kinetic alterations of types I and III collagen were analyzed under polarized light microscope using Sirius Red stain. The hydroxyproline (Hyp) content was measured in the pulmonary tissue after digestion with HCl. A-II radiation immunoactivity (RIA) was assayed in pulmonary tissue homogenate. Pulmonary NO content, NO synthase (NOS), and the angiotensin converting enzyme (ACE) activities were also measured. Our results showed that types I and III collagen genes began to be expressed 1 month after irradiation. Type I collagen gene increased significantly, reaching its peak 3 months after irradiation. As the irradiation dosage was increased from 15 to 30 Gy, the type I collagen gene content increased significantly, while type III significantly decreased. The Hyp content increased with the passage of time after irradiation. Pulmonary A-II RIA increased significantly with the dose of irradiation and was chiefly produced by fibroblasts and macrophages in the interstitium, bronchiolar epithelium, and the anteriolar wall. Pulmonary NO and NOS activities decreased following irradiation. One month following irradiation, the expression of the type I collagen gene begins to increase, with a significant increase in both Hyp and type I collagen 3 months after irradiation. The histogenesis of RPF may be related to A-II. The interstitial cells, the bronchiolar epithelium, and the arteriolar wall can produce A-II and need not pass through the ACE pathway. Our results suggest that the A-II increase and NO decrease may have a role in the pathogenesis of RPF.