Giraffe Skin Disease (GSD) is a newly observed condition mainly affecting adult and sub-adult giraffes in Ruaha National Park (RNP). For the first time, the disease was observed at Lunda, northeastern part of RNP in November 2000 but the disease was thought to have existed for some time. A seasonal variation in the prevalence has also been observed with more animals being affected during the rainy season compared to those affected in the dry season. This study was undertaken with the goal of determining whether: this emerging skin disease has the potential to threaten the persistence of giraffe populations in Ruaha; to highlight epidemiological potential risk factors for the disease and if the disease is associated with mortality or significant morbidity. The study also aimed at assessing the possible routes of transmission, including the role of insect or possibly domestic animals and, where possible, to identify causative agent (s) for Giraffe Skin Disease (GSD). A total of 109 giraffes were examined and 12 others were immobilized, closely examined and sampled for further laboratory analysis. Overall, the prevalence of GSD in RNP was found to be 80% with males observed to be more affected (51.4%) than females (48.6%) (OR 0.32; P=0.049). This investigation has identified a spirurid nematode worm as possible causative agent based on findings of histopathological examination of skin biopsies from affected animals. Although some rod-shaped bacteria and fungi were also isolated, both of them are believed to be secondary invaders after primary infection by the nematodes. Almost all (98.6%) 109 animals examined were equally affected in their both left and right forelimbs with very small involvement of other body parts. Nearly all (99%) of the cases were chronic and more than half (51.7%) of the animals were severely affected by the disease. While most of the animals (89.7%) had normal gait, few others were walking carefully, with stiff or lame gait (2.9%, 4.4% and 2.9%, respectively). At the moment, this disease has been reported in Tarangire and Manyara and Serengeti National Park but its prevalence and dynamics are yet to be identified. It seems the disease is spreading slowly in other ecosystems. It is urgent that we understand the consequences of this disease in terms of the ecology, virulence, morbidity and its potential as a zoonosis. There are several crucial questions that need immediate attention and several measures are proposed as a the way forward including further studies to ascertain the definitive causative agent(s), identify predisposing and other associated factors which led to the development of GSD and finally develop intervention strategies if need arise. Specifically, there is a need to: isolate, characterize and determine the eco-geography of the spirurid nematodes observed in the skin biopsies of the examined giraffes; determine the life cycle of the spirurid Nematode and determine the weak points for intervention; study ranging behaviour, habitat preference and utilization by giraffes and try to link it with the observed disease, and lastly, study the pathogenesis and carry out treatment trials to a few affected and unaffected animals. The data generated by this study supplemented with the currently proposed studies will be helpful to wildlife conservationists. Such information will help monitor the impacts of this disease to the wider conservation of giraffe and possibly other species in protected and non-protected areas of Tanzania. Consequently, these studies will positively contribute in designing appropriate disease mitigation or control strategies nationally, regionally and globally.