To explore the relationship between sperm measures and reproductive success in the laboratory rat, results of several male reproductive toxicology studies containing both fertility and multiple endpoint data are reviewed. Comparisons are made between subchronic and acute exposure studies, stressing the value of multiple endpoint data for each approach. In addition, the choice of endpoints in male reproductive toxicology is discussed with emphasis on those endpoints that are still evolving. The authors conclude that sperm measures are far more sensitive indicators of reproductive organ impairment than is fertility, and that evaluation of multiple endpoints in acute studies is a key step in determining mechanisms of toxicant action that are critical for interspecies risk extrapolation.