The purpose of this investigation was to determine the effect of ethanol on the absorption, excretion and protein binding of sulfadimethoxine from the small intestine of the rat and rabbit. The results are as follows: 1. The rat small intestinal absorption of sulfadimethoxine was increased by 0.5% and 2% ethanol. 2. Blood level of sulfadimethoxine after oral administration was significantly elevated (p<0.01) by 0.5g/kg and 1g/kg ethanol respectively, but was significantly inhibited by 3g/kg ethanol from that of the control. 3. Ethanol gave the effect on the clearance of sulfadimethoxine, which was increased by ethanol from that of control. 4. In the protein binding rate, it was found that ethanol decreased protein binding of sulfadimethoxine except 0.1% and 0.5% ethanol.