To anesthetized rabbits 6-[D-2-amino-2-(cyclohexa-1,4-dienl-yl)-acetamido]-penicillanic acid (epicillin, Spectacillin) and ampicillin were administered i.v. at doses of 50, 100 and 200 mg/kg, and up to 5 to 8 h thereafter the concentration was estimated in the plasma, urine and bile. Within 5 h, the blood levels took biexponential courses so that a two-compartment open model could be assumed. With epicillin all the different doses a more slowly decreasing tissue level and a higher total volume of distribution are obtained as well as a tissue volume of distribution higher than that with ampicillin. The clearance shows that both antibiotics are eliminated in the urine by glomerular filtration as well as tubular secretion and reabsorption. After 200 mg/kg of either antibiotic a three-compartment open model could be assumed, on the base of which only the volumes of distribution for epicillin could be completely determined. The total volume and the tissue volume of distribution are the same after each different dose of epicillin, whilst in the case of ampicillin both volumes are smaller and decrease with rising doses.