The forage tree legume leucaena [Leucaena leucocephala (Lam.) de Wit ssp. glabrata (Rose) Zarate] is a high-quality ruminant feed vitally important as a source of protein for livestock production in tropical regions. However, the presence of the acutely toxic nonprotein amino acid mimosine in leaves and seeds, and its breakdown to chronically toxic hydroxypyridones (DHP), was believed to limit its productivity and adversely affect animal health. The Australian development of a fermenter-cultured oral inoculum containing the DHP-degrading ruminal bacterium Synergistes jonesii in the 1980s was thought to overcome this issue; however, anecdotal evidence of leucaena toxicity symptoms occurring in inoculated animals remained. In response, a program of research was initiated to investigate the efficacy of S. jonesii as well as other methods of protection against toxicity in ruminants. Broadly, this involved two areas of research, namely the effectiveness of: (a) microbiological degradation via S. jonesii; and (b) non-microbial metabolic detoxification. Key objectives were to: (a) determine the efficacy of inoculation with S. jonesii both within Indonesia and Australia; (b) profile the toxicity status of ruminants in eastern Indonesia; (c) investigate the impact of mineral supplementation on 2,3-DHP toxicity; and (d) determine the extent of in vivo conjugation of DHP and its role in protecting ruminants against toxicity. Initially, an Indonesian study involving the transfer of rumen fluid from "protected" ruminants to naïve Bali bulls was conducted. Sequential monitoring of DHP levels in urine indicated that there was no effect of inoculation. Secondly, a controlled animal house experiment was conducted in Australia to measure the impact of high leucaena diets on production in naïve steers and the effect of inoculation with the commercial S. jonesii inoculum. Key findings were: (1) inoculation had no effect on total DHP excretion; (2) indigenous S. jonesii strains were present in naïve animals prior to inoculation; (3) DHP did not suppress thyroid hormone production; and (4) high levels of the isomer 2,3-DHP were present without accompanying signs of toxicity. The leucaena toxicity status of ruminants in eastern Indonesia was then assessed in a survey across the four islands of Lombok, Sumbawa, Sumba and West Timor. A number of different strains of S. jonesii, including the ATCC type strain (78.1), were detected, however S. jonesii was always at low population levels and always accompanied by high levels of undegraded 2,3-DHP in urine. Despite this apparent failure of S. jonesii to degrade DHP, there was no observed impact on animal productivity or health. Accordingly, vii Contributions by others to the thesis This thesis is the original work of Michael Halliday.