An occupational disease in tobacco cultivating farmers has been reported in Florida, North Carolina, and India. This disease is termed "Green-tobacco sickness" with characterized symptomsdizziness, nausea, and generalized weakness. The symptoms develop after the exposure to wet and raw tobacco leaves, and are probably caused by absorption of nicotine through the skin from the leaves. No case of this disease has been reported in Japan until now. In the present study, two cases of the disease were detected in the southern part of Kumamoto Prefecture. These cases, who were tobacco harvesters, have exhibited the "green symptoms" after cropping wet tobacco leaves every year since 7-8 years ago. One was a man aged 55, the other a 42-year-old woman. They were non-smokers and non-drinkers. These cases were diagnosed as the Green-tobacco sickness by the following reasons: 1) They showed the characteristic symptoms of the disease after cropping tobacco leaves in rainy days. 2) Those symptoms have repeatedly observed since 7-8 years ago under the same circumstances; i.e., they handled wet and raw tobacco leaves without rain coats, and were exposed to dew on tobacco leaves. They had no evidence to handle any other toxic substances at that time. 3) The symptoms usually disappeared on the next morning. 4) Food poisoning was neglected. 5) Efforts to avoid the contact with wet tobacco leaves made them free from the disease. An additional experiment using animals revealed that minimum toxic dose of nicotine through the skin was less than 21 mg/kg of body weight in the rat. Furthermore, analysis of the literatures on the Green-tobacco sickness permitted the suggestion that the toxic dose of nicotine through the skin in humans might be less than 1.96 mg/kg of body weight.