Paracetamol causes extensive liver damage when taken in overdose quantities; however, it is less hepatotoxic when administered in combination with caffeine. The present work in mice was undertaken to study the effect of caffeine on mortality rates and biochemical and histological parameters of liver damage after administration of toxic doses of paracetamol. It was found that caffeine markedly increased the survival rate after administration of a dose of paracetamol that was lethal to 50% and 100% of mice, reduced liver damage as assessed by serum glutamic pyruvic and glutamic oxaloacetic transaminase activities, partially prevented the depletion of reduced glutathione and reduced histological changes to the liver accompanying paracetamol intoxication. The results support the possibility that caffeine might be useful for the treatment of paracetamol intoxication in humans.