As an approach to elucidating the roles of interferon (IFN) in the normal physiology and diseases of animals, transgenic mice carrying extra mouse IFN-beta genes under the control of a mouse metallothionein I enhancer-promoter were constructed. Upon induction with Cd2+, IFN activity (15-430 IU/ml) was detected in the sera of six out of ten transgenic mouse lines so far obtained. Synthesis of mRNA of the transgene was observed in the liver, the testis and less abundantly in the brain. Interestingly, IFN mRNA was constitutively synthesized in the testis where substantial levels of IFN accumulated without heavy metal induction, whereas synthesis in the liver was mostly dependent on induction by CD2+. Since IFN activity in the serum also depended on heavy metal induction, the IFN in the serum may be produced mainly in the liver. All males expressing the IFN gene in the testis were found to be sterile. Testes were involuted and contained few mature sperm, and degeneration of spermatocytes and spermatids was observed. These findings suggest that high levels of IFN are harmful to spermatogenesis and can cause male sterility.