A nonhuman primate model of tuberculosis that closely resembles human disease is urgently needed. We have evaluated the Philippine cynomolgus monkey, Macaca fasicularis, as a model of TB. Cynomolgus monkeys challenged intratracheally with extremely high doses of Mycobacterium tuberculosis (10⁵ or 10⁴ CFU) developed an acute, rapidly progressive, highly fatal multilobar pneumonia. However, monkeys challenged with moderate or low doses of M. tuberculosis (≤10³ CFU) developed a chronic, slowly progressive, localized form of pulmonary TB, akin to the disease in humans, that was frequently accompanied by such clinical syndromes as ocular tuberculosis, meningitis and tuberculous spondylitis. A significant proportion of monkeys challenged with 10² or 10¹ CFU contained the infection in a subclinical state. The Philippine cynomolgus monkey model is an excellent model of chronic TB and provides an opportunity to study subclinical and potentially latent disease in an animal model.