The potential neuroprotective effects of guanidinoethane sulfate (GES) on delayed neuronal death of hippocampal CA(1) neurons were investigated using a gerbil model of forebrain ischemia. Neuronal densities of CA(1) neurons in the saline control group (255.1 +/- 11.7 cells/mm) and guanidinoethane sulfate pretreated control group (249.0 +/- 9.4 cells/mm) showed no significant differences. By contrast, in animals subjected to ischemia, CA(1) neurons of the guanidinoethane sulfate pretreated group showed a significantly higher number of surviving neurons (61.1 +/- 55.11 cells/mm) compared to the saline group (17.75 +/- 12.73 cells/mm) (p < 0.05, t-test). The study indicated that although partial, guanidinoethane sulfate is neuroprotective towards gerbil hippocampal CA(1) neurons against ischemic insult.