Cytoprotection by glycine (GLY) in ischemic or reoxygenated renal tissue has well been documented. In cardiomyocytes GLY has been reported to be cytotoxic as well as cytoprotective. We compared GLY-effects in vitro in two freshly prepared cell types: a) isolated rat ventricular cardiomyocytes (IVC) and isolated tubular segments (ITS) of rat kidney cortex. Parameters of cellular integrity were losses of marker enzymes (cytosolic LDH, mitochondrial GlDH). Cell viability was judged by trypane blue staining (TBS) and intracellular potassium accumulation (K+). IVC and ITS were suspended substrate-free at 37°C, gassed 30 min with N2 and subsequently reoxygenated for 30 min. In a concentration range of 1 - 10 mM GLY suppressed maximally (>80%) TBS and LDH/GlDH-losses in both cell types. At > 10 mM GLY, however, in IVC but not in ITS significant cytotoxic effects occurred: TBS and enzyme leakage rose by more than 60%. Concomitantly, at low GLY concentration (< 10 mM) K+ was significantly supported in both cell types. At 100 mM GLY K+ was suppressed in IVC by 32%. TBARS-formation occurred independently of GLY indicating no significant participitation of TBARS-sensitive lipid peroxidation in the GLY-protective mechanism. It is concluded that controversial data about GLY effects in cardiomyocytes may have originated from dose-dependency, GLY being cytoprotective up to 10 mM and becoming cytotoxic at concentrations >10 mM.