Background/Aims: Relationship between gastric alcohol dehydrogenase (GADH) activity and first- pass metabolism of alcohol and the age-dependent changes in hepatic alcohol metabolism are reported. This study was performed in order to demonstrate the differences in the activities of GADH and hepatic alcohol dehydrogenase (LADH) in different aged-groups of Sprague-Dawley rats. Methods: Total 96 rats (16 rats/group, M:F=8:8) were included and their ADH activities were measured. Results: In 15-week-old male rats, Vmax and Km of GADH were 2.32 mM/L/min and 26.11 mM, respectively. Those of LADH were 33.84 mM/L/min and 22.51 mM, respectively at 2.8 mM of nicotineamide adenine dinucleotide. The GADH activities (mean±SD) were 1.30±0.85 in 1 week- old-rats, 2.61±0.96 in 4 week-old-rats, 5.25±1.86 in 10 week-old-rats, 2.31±1.36 in 15 week-old- rats, 2.87±1.15 in 20 week-old-rats, and 3.84±1.72 for 30 week-old-rats, respectively. Meanwhile, the LADH activities were 29.0±4.25 in 1 week-old-rats, 63.16±10.23 in 4 week-old-rats, 45.70±5.66 in 10 week-old-rats, 46.49±10.83 in 15 week-old-rats, 38.85±10.79 in 20 week-old-rats, and 40.59±11.28 in 30 week-old-rats, respectively. These results showed significant age-dependent differences in both GADH and LADH activities (p<0.01). Conclusions: There are significant age- dependent differences in the both GADH and LADH activities and thus, it can be suggested that the age could affect the first-pass metabolism and hepatic metabolism of alcohol. (Kor J Gastroenterol 1999;34:756 - 763)