Expression of the int2/Fgf-3 gene occurs during normal embryonic development and is associated with mammary cancer in mice. Overexpression of this gene under the control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) in males was reported to result in prostatic enlargement. In this report male Fgf-3-overexpressing mice were shown to have enlarged ampullary glands, seminal vesicles, and ductus deferens; there was extensive epithelial hyperplasia in the ampullary glands and seminal vesicles. The prostates of these animals were of normal size and histology. The transgene was expressed in all of the enlarged organs, which are derived exclusively from the Wolffian duct. Male secondary sex organs derived from the urogenital sinus, e.g., the ventral prostate, coagulating gland, and bulbourethral glands, were normal and did not express the MMTV-LTR-driven Fgf-3 transgene. A dorsolateral prostate was also morphologically normal but did express the transgene. This study underscores the importance of careful organ identification in transgenic models in which gross organ enlargement or distortion occurs. It also highlights the heterogeneity of the response to Fgf-3 among the secondary sex organs and even within the prostate itself.