The organism that causes leprosy is a rod-shaped bacterium called Mycobacterium leprae. This bacterium is related to Mycobacterium tuberculosis, the causative agent of tuberculosis. Because special staining techniques involving acids are required to view these bacteria under the microscope, they are referred to as acid-fast bacilli (AFB).

When Mycobacterium leprae invades the body, one of two reactions can take place. In tuberculoid leprosy (TT), the milder form of the disease, the body's immune cells attempt to seal off the infection from the rest of the body by surrounding the offending pathogen. Because this response by the immune system occurs in the deeper layers of the skin, the hair follicles, sweat glands, and nerves can be destroyed. As a result, the skin becomes dry and discolored and loses its sensitivity. Involvement of nerves on the face, arms, or legs can cause them to enlarge and become easily felt by the doctor. This finding is highly suggestive of TT. The scarcity of bacteria in this type of leprosy leads to it being referred to as paucibacillary (PB) leprosy. Seventy to eighty percent of all leprosy cases are of the tuberculoid type.

In lepromatous (LL) leprosy, which is the second and more contagious form of the disease, the body's immune system is unable to mount a strong response to the invading organism. Hence, the organism multiplies freely in the skin. This type of leprosy is also called the multibacillary (MB) leprosy, because of the presence of large numbers of bacteria. The characteristic feature of this disease is the appearance of large nodules or lesions all over the body and face. Occasionally, the mucous membranes of the eyes, nose, and throat may be involved. Facial involvement can produce a lion-like appearance (leonine facies). This type of leprosy can lead to blindness, drastic change in voice, or mutilation of the nose. Leprosy can strike anyone; however, children seem to be more susceptible than adults.

Well-defined skin lesions that are numb are the first symptoms of tuberculoid leprosy. Lepromatous leprosy is characterized by a chronic stuffy nose due to invasion of the mucous membranes, and the presence of nodules and lesions all over the body and face.

Although patients with leprosy are commonly thought not to suffer pain, neuroapthic pain caused by inflammation of peripheral nerve endings is increasingly recognized as a major complication of the disease in many patients. Corticosteroids may be given to reduce the inflammation.

The incubation period of the leprosy bacillus varies anywhere from six months to ten years. On an average, it takes four years for the symptoms of tuberculoid leprosy to develop. Probably because of the slow growth of the bacillus, lepromatous leprosy develops even more slowly, taking an average of eight years for the initial lesions to appear.

It is still not very clear how the leprosy bacillus is transmitted from person to person; about 50% of patients diagnosed with the disease have a history of close contact with an infected family member. Since untreated patients have a large number of M. leprae bacilli in their nasal secretions, it is thought that transmission may take place via nasal droplets. The milder tubercular form of leprosy may be transmitted by insect carriers or by contact with infected soil.

The incidence of leprosy is highest in the poverty belt of the globe. Therefore, environmental factors such as unhygienic living conditions, overpopulation, and malnutrition may also be contributing factors favoring the infection.

It is also possible that genetic factors are involved in susceptibility to leprosy. In 2003, scientists conducting a genome scan of a large Vietnamese family with many cases of leprosy found that susceptibility to the disease was linked to region q25 on the long arm of chromosome 6. Further study indicated that the leprosy susceptibility gene lies within a region shared by two genes for Parkinson's disease. Further research may confirm that the emergence of leprosy in certain individuals is related to inheritance of genes for Parkinson's disease.