In female nude mice, epidermal growth factor (EGF) was present at a mean concentration of 42.8 +/- 16.9 (SD) ng/mg wet tissue in the submandibular gland and 0.28 +/- 0.13 ng/ml in the plasma. Sialoadenectomy (removal of the submandibular glands) decreased circulating EGF to undetectable levels (less than 0.1 ng/ml). The possible role of EGF in transplantation and growth of mouse mammary tumors in nude mice was examined by sialoadenectomy, anti-EGF treatment, and EGF replacement therapy. The success rate of transplantation of a spontaneous mouse mammary tumor into nude mice was 55% in normal females and 17% in sialoadenectomized animals. Anti-EGF treatment of sialoadenectomized mice completely abolished the implantation of the tumor. Daily administration of EGF at a dose of 5 micrograms per mouse to both normal and sialoadenectomized animals enhanced the success rate of tumor implantation to more than 80%. Sialoadenectomy and/or anti-EGF treatment of tumor-bearing nude mice reduced the growth of implanted mammary tumors. These results suggest that EGF is important for implantation and growth of spontaneous mouse mammary tumor in female nude mice.