The purpose of this study was to examine the relative influence of such factors as age, gender, and absolute force on the fatiguability of the human adductor pollicis muscle. 12 young males (YM, 25.3 +/- 2.1 y), 12 young females (YF. 23.5 +/- 2.1 y), 12 older males (OM, 71.7 +/- 5.6 y) and 12 older females (OF, 69.5 +/- 4.6 y) participated. Three minutes of intermittent (5 s contraction, 2 s rest) maximal voluntary contractions (MVC) were used to fatigue the adductor pollicis muscle; the ulnar nerve was also stimulated in each 2 s rest period to evoke a maximal twitch. Males were stronger than females in both voluntary and evoked force (PT) in the young age group (MVC: YM, 10.0 +/- 2.7 kg vs. YF, 6.6 +/- 1.1 kg, P < 0.05) (PT: YM, 0.99 +/- 0.21 kg vs. YF, 0.71 +/- 0.12 kg, P < 0.05). In the older adults, however, males were stronger only in the evoked twitch (OM, 0.73 +/- 0.24 kg vs. OF, 0.48 +/- 0.07 kg, P < 0.05). There was no significant effect of gender or absolute muscle force on relative fatigability; the only variable found to significantly affect fatigability was age. Older adults were significantly less fatigable than young adults as indicated by the voluntary fatigue index (FI) (percentage of force reduction from baseline; FI-young, 40.2 +/- 12.6% vs. FI-old, 25.2 +/- 12.3%). This age effect, however, was more prominent in males than females (FI-YM, 44.7 +/- 10.5% vs. FI-OM, 24.2 +/- 10.7%, P < 0.01; FI-YF, 37.8 +/- 14.1% vs. FI-OF, 26.3 +/- 14.5%, P = 0.13). In conclusion, age was found to be the strongest single predictor of fatigability during short duration, intermittent exercise in human adductor pollicis muscle.