Materials and Methods Young male New Zealand white rabbits, weighing between 1.0 and 1.5 kg, were used in the study. They were kept in individual cages, fed Purina laboratory chow, and had free access to water. The test compounds included indole, skatole, tryptophan, kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, nicotinic acid and nicotinamide, as well as oxindole, isatin and indican, 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Various amounts of each compound were prepared either in aqueous 50% propylene glycol or in 0.9% NaCl solution depending on their solubility. Saline solutions of acidic compounds were neutralized with NaOH. One ml of the sterile test solution was injected aseptically into the joint cavity of one hind knee. For control purposes, either aqueous 50% propylene glycol or 0.9% NaCl solution was injected into theother knee joint. The rabbits were sacrificed by cervical fracture and were immediately autopsied. The bind legs were removed and examined grossly and microscopically. Tissues from various visceral organs and from all injected joints and para-articular structures were fixed in 10% neutral formalin and bone specimens were decalcified in Decal.'Tissues were imbedded in paraffin, 5, u sections were cut and stained with hema-toxyln and eosin (H&E), and, whenever indicated, with Masson's trichrome, Putt's and periodic acid-Schiff (PAS) stains. Experkment 1. Five rabbits were injected with a single dose of indole (0.263 mmol) prepared in 1.0 ml of aqueous 50% propylene glycol, and another 5 were Minectd with a simila preparation of skatole. The rabbits were sacrificed 1, 2, 3, 4, and 7 days after the injection. Experiment 2. Six rabbits were injected with one of the following amounts of indole: 0.04, 0.08, 0.13, 0.17, 0.21 and 0.26 mmol respectively. Another 6 rabbits were treated similarly with skatole. The injections were repeated once a week for 6 weeks. All animals were sacrificed 8 weeks after the initial injection. Experiment 3. Fourteenrabbits were injected with 0.1 mmol of one of 14 test compounds (Text-fig 1). Theinjections were repeated once a week for 6 weeks. All animals were sacrificed 8 weeks after the initial injection. Experiment 4. The skin on the back of one rabbit was shaved and 0.2 mmol of indole in aqueous50% propylene glycol was injected intracutaneously. Intra-cutanous injection of solvent served as a control.