Radiation and chemotherapy reduce sperm count and cause infertility in males. In the mouse, rat, and human, the differentiating spermatogonia are the most sensitive to killing by cytotoxic agents, resulting in short-term azoospermia. Stem spermatogonia are also killed by some agents. In the mouse, sperm production gradually recovers from surviving stem cells without a lag period. In the rat, however, surviving stem cells may remain as A spermatogonia for long times without initiating differentiation. In humans, there may be a long period of azoospermia; the time at which recovery or sperm production is initiated appears to be related to the degree of stem cell killing. Knowledge of the mechanisms regulating spermatogonial proliferation and differentiation could lead to ways to minimize the duration of azoospermia following treatment.