The ability of 7 antibiotics (carbenicillin, cloxacillin, ampicillin, cephalothin, cephaloridine, cefoxitin and fosfomycin) to enter interstitial tissue fluid was evaluated. Using rabbits with implanted subcutaneous chambers, antibiotics were given i.m. as a single dose of 15 mg/kg and antibiotic levels in serum and interstitial fluid of the chambers were determined at variously scheduled times after injection. Antibiotic concentrations in the 2 compartments apparently did not run parallel. Antibiotic diffusion from blood to interstitial fluid generally increased with the concentration gradient and serum half-life, and there was an inverse relationship to pKa, protein binding and MW of the antibiotic.