The role of glucose metabolism in sperm cell motility was examined in purified human spermatozoa from the perspective of elucidating its possible significance in spontaneous and experimental diabetes. After a 4-h incubation in the absence of D-glucose, the mean progressive velocity of human spermatozoa was 40% lower than that of control cells kept in the presence of D-glucose. The decline was rapidly overcome by the addition of D-glucose or D-fructose, the amplitude of this stimulatory effect being independent of the ambient hexose concentration. Between 1.4 and 16.7 mM glucose, spermatozoal glucose oxidation also proceeded independently of the extracellular glucose levels, whereas both insulin (100nM) and glucagon (100nM) failed to significantly affect the rate of glucose metabolism or cellular motility. It is speculated from these results that an alteration in seminal hexose concentrations or pancreatic hormone levels may be an unlikely cause for the reduced sperm motility that is characteristically observed in diabetic patients. Human spermatozoa rapidly incorporated D-glucose and 3-O-methyl-D-glucose but excluded the glucose-analogue alloxan, which may explain their resistance against the toxic effects of this diabetogenic drug, in spite of their intrinsic sensitivity to organic peroxides such as tert-butyl hydroperoxide.