Protein is the macronutrient that induces the strongest feeling of satiety. Protein-induced satiety may be mediated by the specific amino acids generated by protein digestion. We have identified L-cysteine as an amino acid with anorexigenic properties. Food intake was measured in overnight fasted male Wistar rats, following oral gavage of water, 1, 2 or 4mmol/kg L-cysteine and a conditioned taste aversion protocol employed to investigate the possibility of treatment associated consequences. Subsequently, rats received an oral gavage of water or 4mmol/kg L-cysteine and 30 minutes post administration were culled by decapitation and trunk blood collected. Plasma levels of insulin and the anorexigenic hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured by radioimmunoassay, and plasma levels of the orexigenic hormone acyl-ghrelin were measured by an enzyme immunoassay. The effect of repeated administration of L-cysteine on food intake was also investigated. All data are expressed as mean ± sem. Oral gavage of 2 and 4mmol/kg L-cysteine significantly reduced food intake compared to water control in the 0-1 hour period following administration (water: 6.8 ±0.6g vs. 2mmol/kg L-cysteine: 4.3 ± 0.6g, p<0.05; vs. 4mmol/kg L-cysteine: 2.7 ± 0.3g, p<0.001, one-way ANOVA, n=7-8). Doses of L-cysteine that reduced food intake did not induce any aversive behaviour suggesting the reduction in food intake was not secondary to unpleasant post-ingestive consequences. L-cysteine significantly reduced plasma acyl-ghrelin levels 30 minutes post administration compared to water control (water: 8.8 ± 1.6pmol/l vs. L-cysteine: 3.6 ± 0.9pmol/l, p=0.019, t-test, n=7-8) and significantly increased plasma insulin levels compared to water control (water: 68.0 ± 7.7pmol/l vs. L-cysteine: 125.7 ± 20.7pmol/l, p=0.020, t-test, n=8). However, there was no effect on plasma GLP-1 or PYY levels. Repeated administration of L-cysteine over 5 days significantly reduced cumulative food intake compared to water and glycine (negative control) treated controls (day 5, water: 144.7 ± 3.5g, glycine: 145.7 ± 3.0g, vs. L-cysteine: 130.1 ± 2.5g, p<0.001, two-way ANOVA, n=6-9). L-cysteine may therefore contribute towards protein induced satiety by suppressing the release of the orexigenic hormone ghrelin. Altering the amino acid content of foods may represent a possible intervention to manipulate appetite.