We performed two studies to determine the effect of a resistive training program comprised of fast vs. slow isokinetic lengthening contractions on muscle fiber hypertrophy. In study I, we investigated the effect of fast (3.66 rad/s; Fast) or slow (0.35 rad/s; Slow) isokinetic high-resistance muscle lengthening contractions on muscle fiber and whole muscle cross-sectional area (CSA) of the elbow flexors was investigated in young men. Twelve subjects (23.8 +/- 2.4 yr; means +/- SD) performed maximal resistive lengthening isokinetic exercise with both arms for 8 wk (3 days/wk), during which they trained one arm at a Fast velocity while the contralateral arm performed an equivalent number of contractions at a Slow velocity. Before (Pre) and after (Post) the training, percutaneous muscle biopsies were taken from the midbelly of the biceps brachii and analyzed for fiber type and CSA. Type I muscle fiber size increased Pre to Post (P < 0.05) in both Fast and Slow arms. Type IIa and IIx muscle fiber CSA increased in both arms, but the increases were greater in the Fast- vs. the Slow-trained arm (P < 0.05). Elbow flexor CSA increased in Fast and Slow arms, with the increase in the Fast arm showing a trend toward being greater (P = 0.06). Maximum torque-generating capacity also increased to a greater degree (P < 0.05) in the Fast arm, regardless of testing velocity. In study II, we attempted to provide some explanation of the greater hypertrophy observed in study I by examining an indicator of protein remodeling (Z-line streaming), which we hypothesized would be greater in the Fast condition. Nine men (21.7 +/- 2.4 yr) performed an acute bout (n = 30, 3 sets x 10 repetitions/set) of maximal lengthening contractions at Fast and Slow velocities used in the training study. Biopsies revealed that Fast lengthening contractions resulted in more (185 +/- 1 7%; P < 0.01) Z-band streaming per millimeter squared muscle vs. the Slow arm. In conclusion, training using Fast (3.66 rad/s) lengthening contractions leads to greater hypertrophy and strength gains than Slow (0.35 rad/s) lengthening contractions. The greater hypertrophy seen in the Fast-trained arm (study I) may be related to a greater amount of protein remodeling (Z-band streaming; study II).