Hyperammonaemia, an excess of ammonia in blood and/or tissue, is believed to contribute to the neuropsychological disturbances observed in liver disease patients, through disruption to the cellular processes within brain linked to cognitive and motor function (Cauli et al., 2009). Hyperammonaemia can also be observed in healthy conditions, such as in exercise, where levels can often reach or exceed those of disease states. Therefore, it has been proposed that hyperammonaemia may be an important component in fatigue development, acting through similar mechanisms as disease (Wilkinson et al., in press). The aim of this study was to investigate whether an acute state of hyperammonaemia in healthy resting adults would induce sensations of fatigue, whilst also affecting aspects of cognition and motor control. Nine healthy males (Age: 23 ± 5yrs, Mass: 77 ± 7kg; Height: 179 ± 4cm; Mean ± SD), after providing written informed consent, received two 4 hr intravenous infusions of either a 2% ammonium chloride solution (AMM) or a placebo (PLA; 0.9% sodium chloride solution), administered at a constant rate of 90ml/hr using a double blind cross-over design. Sensations of fatigue during each infusion were measured at baseline, 2 and 4hrs using the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) questionnaire. Arterialised venous blood samples were collected every hour, and plasma ammonia concentrations measured using spectrophotometry. Assessment of learning & memory, motor control and cognition were performed using Rey’s Auditory Verbal Learning Test (AVL; Lazek et al., 2004), the Compensatory Tracking Task (CTT; Makeig and Jolley, 1996) and The Inhibitory Control Test (ICT; Garavan et al., 1999) respectively. Data are presented as mean ± SEM. Differences in plasma ammonia concentration, CTT and ICT task performance were analysed by ANOVA, AVL data by paired t-test, and MFSI-SF by Wilcoxon signed rank test. Plasma ammonia concentrations were significantly increased (from 52 ± 6µmol/l at baseline to a peak of 234 ± 11µmol/l at 2 hours, F=379.175, p < 0.001) in the AMM trial. At 2 hours there was a significantly higher total MFSI-SF score in the AMM trial compared to the PLA trial (Z = -2.371, p = 0.008, 1 tailed). Which when the individual subscales were analysed, showed significantly higher sensations of general fatigue (Z=-2.375, p=0.008, 1 tailed) and physical fatigue (Z=-1.914, p=0.027, 1 tailed), and lower sensations of vigour (Z=-2.257, 0.012, 1 tailed). There were no differences observed in the remaining two subscales of mental (Z=-1.556, p=0.084, 1 tailed) or emotional fatigue (Z=-0.184, p=0.500, 1 tailed). In addition, there were no significant effects on the performance of any of the psychological tasks. These findings suggest that acute hyperammonaemia may induce sensations of fatigue in the absence of affects on psychological task performance.