The possibility of activated charcoal interrupting the enteroenteric circulation of phenobarbital was conducted in rabbits prepared by colectomy biliary drainage to block enterohepatic circulation. Fifty minutes after the administration of phenobarbital IV over ten minutes, activated charcoal (N = 7) or non-adsorbent gel (N = 8) were placed into the intestine at a dose of 4 g/kg. Blood was taken hourly for 5 h from the femoral artery and portal vein for the determination of phenobarbital concentration by the homogeneous enzyme immunoassay. The arterio-portal differences of phenobarbital concentrations were significantly greater in the animals treated with the charcoal at 2, 3 and 4 h after the treatment. There were significantly shorter plasma half lives of phenobarbital in the animals given charcoal (3.8 +/- 0.3 h vs 6.9 +/- 0.9 h, p < .02). This study provided evidence of significant enteroenteric circulation of phenobarbital which can be interrupted by the activated charcoal and removed by the mechanism of intestinal dialysis.