The effects of radiation on gut mucosal mast cells (MMC) and tissue eosinophils were examined. Groups of rat were given single doses of whole-body irradiation from 0.5 to 5 Gy. Serum rat mast cell protease II (RMCPII) concentration showed a significant dose-dependent fall after 1 Gy on day 3 and 1.5 Gy on day 7. MMC counts and tissue RMCPII values on day 7 decreased significantly by 70% after 1 Gy and were undetectable with larger doses. Rat with normal and expanded MMC populations were irradiated or given anaphylaxis. Serum RMCPII concentrations did not change after irradiation, but there was a 10-fold increase in RMCPII after anaphylaxis. Tissue eosinophils in jejunum were 50% of control at 7 days after 2 Gy, and this effect was progressively more marked with higher doses. Similar effects on MMC and eosinophils were demonstrated in ileum, ascending colon and rectum. After 4.5 Gy, repopulation of the gut with MMC did not occur until week 3-4 postirradiation and MMC counts were still 50% below those of controls at 5 weeks postirradiation. Counts of tissue eosinophils 5 weeks after 4.5 Gy irradiation had returned to control levels in jejunum but were still significantly depleted in colon. These experiments show that the high radiosensitivity of rat intestinal MMC is dose dependent, similar at four different levels in the gastrointestinal tract and does not lead to immediate release of granule protease; repopulation with MMC does not begin until at 3 weeks postirradiation.