A study was performed in 110 rats to investigate the effect of an LD50 dose of MTX, rescued with leucovorin treatment in 24 hours, on the ability of surgical wounds to tolerate bacterial contamination. The results of this study would indicate that the optimal time to ensure normal wound healing would be an interval of 10 to 14 days following the administration of large doses of this drug. This information would suggest that the use of methotrexate as a preoperative adjuvant, and radiation therapy following the surgical removal of the tumor, might be a reasonable approach to the adjuvant treatment of head and neck cancer without increasing the risk of wound infections.