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 (10(5) or 10(4) CFU) developed an acute, rapidly progressive, highly fatal multilobar pneumonia. However, monkeys challenged with moderate or low doses of M. tuberculosis (</=10(3) 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 10(2) or 10(1) 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.