The effect of incubation with caffeine to a final concentration of 6 mM at seven time intervals from 0 to 120 minutes was examined in spermatozoa from two normal fertile semen samples and two infertile asthenozoospermic men. Light microscopic estimation of motility, scanning electron microscopic examination of the surface morphology and scanning transmission determination of subcellular elemental composition was carried out at each stage in comparison with placebo controls (modified Ringer solution). An interaction with incubation appeared necessary for caffeine to energise spermatozoa. This stimulatory effect on motility was more marked in the abnormal subjects although in all four individual response was variable. Surface morphological damage was noted in all experiments but was more pronounced the longer spermatozoa spent incubated with caffeine. Disruption of the sperm head and swelling of the mid-piece were the most characteristic features. Subcellular elemental composition of all six elements was greater in the fertile than in the infertile samples and caffeine exceeded placebo in four of the six, with a significant difference in sulphur levels. Sodium, sulphur and magnesium showed similar patterns of sub-group measurements at each of the seven time points suggesting perhaps a similar time influence mechanism operating for these three elements. The study shows the detrimental effect of incubation with caffeine to be marked and time linked, the shorter the time of incubation exposure with the drug the better. Therefore not only does the damage created make the incubation with caffeine of any semen sample unwise but the time strictures, especially in the asthenozoospermic, show it also to be an impractical method of increasing pregnancy potential in such subjects.