This laboratory study compared the biomechanical and biochemical healing of microvascular free skin flaps in irradiated and nonirradiated recipient areas. In the adult rat, the skin of the right groin region was exposed to a single fraction dose of 20 Gy, using a linear megavoltage accelerator. The left groin was shielded. One week after radiotherapy, the left femoral artery and vein were divided, and an anastomosis was created in situ at the site of the epigastric pedicle. The epigastric skin flap was crossed over to replace the central area of the irradiated skin in the contralateral right groin. The healing of the interface between the irradiated recipient skin and the transferred free epigastric flap was studied at 4 weeks. A comparison was made with the microvascular free flaps of nonirradiated control animals. An additional group of control animals was used to verify the retarding effect of the 20-Gy radiation dose on wound healing. In control animals, the single dose of 20 Gy decreased the tensile strength of standardized surgical wounds by 23% (p = 0.03). Clinical healing of the transferred microvascular free flaps between the irradiated and control recipient areas was comparable, and the flaps showed no significant differences in the mechanical incorporation. The biochemical assays of the DNA, RNA-ribose, total nitrogen, and hydroxyproline contents of the flap showed an increased concentration of proteins (total nitrogen) expressed per cell count (DNA) (25%, p = 0.04), reflecting the excessive accumulation of organic matrix and a relatively decreased number of cells in irradiated recipient tissues. We conclude that there are no major differences in the healing capacity of microvascular free skin flaps between irradiated and nonirradiated recipient areas.