The penetration of sc fibrin clots by nine antibiotics, administered by rapid iv infusion, was studied in an established rabbit model. After an interval (which varied among different agents), concentrations of drug in fibrin loci exceeded those in serum. Pairs of penicillins with low and high degrees of binding to serum proteins were given in sequence to the same animal. The concentrations in fibrin clots of two weakly bound agents were significantly higher than those of two strongly bound ones, although peak concentrations in the serum were similar. These differences in penetration were directly related to the concentration of free (rather than total) antibiotic in the serum. When the effects of protein binding were excluded, the drugs displayed equal facility of passage from the blood into fibrin loci.