The population collapse of resident Gyps vulture species in South Asia, caused by the use of a veterinary drug diclofenac, has highlighted an urgent need to monitor numbers of other vulture species in the region. This study assessed population trends of Himalayan Griffon Gyps himalayensis in the mountainous region of Upper Mustang, Nepal, which is an important breeding area for the species. Vultures were surveyed in 2002, 2004 and 2005 by recording the number of birds sighted along 188 km of transects, and observing numbers of birds at breeding colonies. The number of birds recorded per day and per kilometre of transect declined by 67% and 70% respectively over the period of study. The number of active nests declined by 84% from 2002 to 2005. The veterinary drug diclofenac was available in pharmacies in the Mustang region. Young Himalayan Griffons, which migrate to the lowland areas of Nepal and, in increasing numbers to India, are highly likely to be subject to diclofenac poisoning. If this rate of population decline occurs throughout the Himalayan region, the conservation status of the species will need to be urgently reassessed.