The human male is of relatively low fertility and thus may be at greater risk from reproductive toxicants than are males of the common laboratory animal model species. Lack of knowledge of the physiological differences that contribute to interspecies variation between man and animals can prevent the effective application of animal data to the assessment of human reproductive risk. Evaluation of spermatogenesis from testicular histology, while uncommon, can provide valuable information about human reproductive risk. The measurement of sperm count or concentration has long been the most feasible approach for human semen evaluation, but may be an insensitive indicator of reproductive function because of high sample-to-sample variability. Interspecies extrapolation factors can be calculated by comparing the reduction in sperm count in humans and test species after exposure to drugs or chemicals. These factors can provide a realistic assessment of relative risk, provided that the sperm are counted at the appropriate time after exposure. However, the degree to which extrapolation factors derived for one agent, and only from sperm counts, can be generalized is not known. Monitoring of sperm motility and morphology parameters is also a common means of evaluating human semen quality, but these techniques are also hampered by the relatively high interindividual and intersample variability. Computer-assisted and morphometric approaches show promise of decreasing the subjective nature of these evaluations and increasing their value in risk assessment procedures. Improvements in predicting human reproductive risk can be expected to come from increased knowledge about reproductive mechanisms in man and animals, together with the utilization of objective measures of cellular indicators of male reproductive function.