In order to study the behavior of two cephalosporines in various tissues, 100 mg/kg of cefoperazone (CPZ) or cefalotine (CLT) were administered intraperitoneally to Wistar rats. The animals were sacrificed by groups of 6 at intervals ranging from 30 min to 6 hours after the injection and bioassay of the antibiotic was carried out in 9 organs, the serum, and urine. There are marked differences in tissue affinity for each antibiotic, as well as between the tow antibiotics. With the exception of the renal medulla, CPZ penetrates most tissues better than CLT. This difference is particularly striking in the liver. The decline of concentrations is nearly the same in tissues and serum; it is 2--3 times slower for CPZ. Concentration of CPZ exceed 1 microgram/g for more than 6 hours in the kidney and 4 hours in the liver, whereas CLT cannot be quantified after 2 hours in the kidney and after 1 hour in the liver. As has been noted for other antibiotics, plasma protein binding has only limited influence on cephalosporin penetration into tissues. This study of pharmacokinetics in tissues shows that CPZ permeates well those tissues where it is supposed to be effective and remains there longer than CLT. The study illustrates a method which provides a better understanding of the mechanisms responsible for antibiotic action.