Utilizing multiperforated capsules implanted in tissue, the concentrations of cephalotin, ampicillin, and tetracycline in soft tissue interstitial fluid (STIF) and renal interstitial fluid (RIF) were measured simultaneously and compared with concentrations found in serum and urine in dogs. Antibiotic concentration in RIF was less than urinary levels but exceeded serum concentrations. A direct time-concentration relationship of these three structurally unrelated antibiotics in serum and renal interstitial fluid was found. This model helps illuminate the basic pharmacokinetics of antibiotic in the renal interstitium where pyelonephritis occurs.