Caffeine is widely spread and well known as a mild stimulant of the central nervous system. The present study tested the role of caffeine and Ruthenium red on the intact neuronal cells alone and Ruthenium red in caffeine-induced neurotoxicity. One-day-old newborn rats were used to obtain cerebellar cell cultures. Caffeine at a concentration of 1 mM was found to be most toxic. Dead cell scores were 5.9 +/- 0.8 for control, and 56.2 +/- 3.4 for caffeine (p < .001). Ruthenium red alone has also caused the reduction in neuronal cell number 361 +/- 4.5 for 10(-5) and 47 +/- 2.7 for 10(-6) M concentrations (p < .001 for both). Interestingly Ruthenium red used in caffeine-induced neurotoxicity has partly diminished the number of dead cells 28.7 +/- 3.2 for 10(-5) and 23.8 +/- 2.27 for 10(-6) M concentrations (p < .001 for both). The results suggest that both Ruthenium red and caffeine are neurotoxic alone but, in combination, the neurotoxicity may be reduced through partial agonistic action.