Temporary sterility is produced by 5-thio-D-glucose when administered in the diet to male mice. We report the effect this compound has on fertility in male rats, a second rodent species, when administered by oral intubation at doses of 50, 25 and 12.5 mg/kg. Weekly cohabitations with proestrous females followed by the number of implants observed at Day 15 of gestation was used to assess male fertility. Permanent sterility with loss of germinal epithelium was produced by 5-thio-D-glucose in male rats when treated for 8 weeks at 50 or 25 mg/kg while a similar regimen was reported reversible in mice. A 14 week treatment period at 12.5 mg/kg was required to produce infertility but the regimen caused sterility in more than half the animals treated. Histological examinations revealed the loss of all germ cells except spermatogonia, and occasionally, primary spermatocytes while Leydig and Sertoli cells and other body tissues appeared normal. With each regimen studied, libido and weight gain were unaffected and of the body organ weights taken, only the testis was reduced.