The existence of circadian variations of the toxicity and effectiveness of Guizhi decoction were investigated in rodents. The result shows a significant circadian rhythm for the toxicity of the drug, with the higher toxicity in the light phase than in the dark phase. A temporal change in the effectiveness of the drug has also been demonstrated with higher analgesic and febrifuge effects in the dark phase. All these suggest that the time factor in drug administration and the principles of chronopharmacology should be included in the consideration of response to the drug.