1. 6-Chloro-6-deoxyglucose (24 mg/kg/day) produces a rapid and reversible antifertility effect in the male rat but high doses (greater than 200 mg/kg/day) produce spermatocoeles. In the mouse repeated high doses (480 mg/kg/day) cause paralysis of the hind limbs but there is no effect on fertility. 2. Spermatozoa from rats treated with 6-chloro-6-deoxyglucose (24 mg/kg/day) are unable to metabolize glucose and rapidly become exhausted when glucose is the only substrate supplied. Glycolysis is inhibited at the glyceraldehyde 3-phosphate dehydrogenase reaction. These spermatozoa can obtain energy by oxidizing pyruvate or lactate. 3. The side effects prevent the use of 6-chloro-6-deoxyglucose by humans but a fuller understanding of their mode of action may lead to the development of compounds with a more selective attack on spermatozoa.