TO examine glutamate-mediated toxic effects in dispersed cultures of the rat cerebral cortex we compared the utility of parameters of cell viability in parallel. A 1 h exposure to glutamate and glutamate analogues (kainate, quinolinate, NMDA) was found to produce typical morphological changes in matured cell cultures. The double-labelling fluorescence technique (fluorescein diacetate/propidium iodide) reflected the degeneration process vividly. A significant increase in LDH-activity released into the medium was noted only when the cells were stressed but still living. When the phase of progressive cell death was running, LDH activity in the medium decreased markedly. Obviously, increasing LDH release in the culture medium must be considered rather to be an indicator for a slowly evolving degenerative process than for cell death.