We have previously shown that following a period of unimanual fatiguing exercise, there is a reduction in primary sensorimotor cortex (SM1) activation with movement of either the fatigued or the non-fatigued hand by Benwell et al. (Exp Brain Res 167:160-164, 2005). In the present study we have investigated whether this reduction is confined to motor areas or is more widespread. Functional imaging was performed before and after a 10-minute fatiguing exercise of the left hand (30% of maximum handgrip strength) in seven normal subjects (4 M, mean age 25 years). The activating task was a handgrip against a low resistance (1 kg) in response to a visual cue (chequerboard reversal every 2 +/- 0.5 s). We compared activation in SM1, supplementary motor area (SMA), cerebellum (CB) and primary visual cortex (V1) before and after the fatiguing exercise. After exercise, contralateral SM1 activation was reduced by 33% (P < 0.05) compared to baseline for the fatigued hand and by 49% for the non-fatigued hand (P < 0.05). A similar pattern was seen for the bilateral SMA and ipsilateral CB following exercise (45 vs. 50% for SMA; 30 vs. 35% for CB; fatigued versus non-fatigued). Activation was also reduced in V1 but to a lesser extent than in motor areas (19 vs. 24%; fatigued versus non-fatigued). These results show that although the reduced functional activation during the recovery period after fatiguing exercise is more marked in motor areas, it also extends to non-motor areas such as the visual cortex, suggesting that there are more widespread changes in cerebral haemodynamic responses after fatigue.