The sulphydryl containing amino acid, L-cysteine has been implicated in myocardial protection (Pisarenko, 1996). In whole hearts, perfusion with the L-cysteine donor, RibCys, increased reduced glutathione levels (Roberts and Francetic, 1991), whilst perfusion with L-cysteine scavenged the hydroxy radical generated during reperfusion of dog hearts following ligation of the left anterior descending coronary artery (Tang et al. 1991). There are very few studies however relating these metabolic improvements to cardiac function with/without L-cysteine. Therefore the aim of this study was to investigate the effect of L-cysteine treatment on functional recovery and membrane integrity following a period of global ischaemia.Male Wistar rats were humanely killed by cervical dislocation. The hearts were dissected and perfused with Krebs at 37°C in the Langendorff mode as described previously (Javadov et al. 2000). After 30 minutes equilibration hearts were exposed for 45 minutes to global normothermic ischaemia followed by 30 minutes reperfusion. In the treated groups 0.5mM L-cysteine was present 10 minutes before and during ischaemia, but was washed out after 10 min reperfusion. During this time cardiac function was measured with a water filled balloon inserted into the left ventricle and connected via a pressure transducer to a Mac Lab. Sarcolemmal integrity during reperfusion was measured from the release of lactate dehydrogenase.During reperfusion, L-cysteine significantly improved the recovery of rate pressure product (RPP) and reduced the release of lactate dehydrogenase (LDH). The percentage recovery of RPP (left ventricular developed pressure x heart rate) was 53.9 ± 11.2% in control hearts compared to 90.9 ± 12.2% in cysteine treated hearts (p < 0.05, Students ttest, n=6-9 ± S.E.). Total LDH release from control hearts was 0.2 ± 0.03 IU/g wet weight compared to 0.05 ± 0.01 IU/g wet weight in the L-cysteine treated group (p < 0.01, Students ttest, n=6-9 ± S.E.). There was also a trend towards a longer time to ischaemic contracture in the cysteine treated group. These results suggest that 0.5mM L-cysteine increased the recovery of isolated rat hearts possibly through an improved metabolism during ischaemia (including maintenance of reduced glutathione levels) and detoxification of free radicals on reperfusion.