An understanding of the absorption of antibiotics from joints was investigated comparing intraarticular (i.a.) absorption with intramuscular (i.m.) absorption in a rabbit knee model. The antibiotics investigated were methicillin, cephalothin, cefazolin, cefoxitin, amikacin, neomycin, kanamycin, and gentamicin. Absorption was measured both in animals in which the knee joint was infected with Staphylococcus aureus and in normal animals. The pattern of absorption was similar among different antibiotics. On an average, antibiotics are absorbed from infected joints 37% slower than from an i.m. injection. In animals that are not infected i.a. antibiotics are actually absorbed 12% faster than i.m. antibiotics. Thus, i.a. antibiotics are absorbed rapidly and similarly to i.m. injection and should be included in total dose calculations for antibiotic regimens, especially with regard to their potential toxicity.