Studies including close contacts of leprosy patients were performed; an inverse relationship between degree and length of exposure to Mycobacterium leprae (MI) and the magnitude of the in vivo specific immune response (Mitsuda reaction) was observed. On the other hand, this variable is greatly influenced by genetic determination. In the experimental adjuvant arthritis model, MI treatment was able to trigger a splenic suppressor cell population with regulatory activity on the immune response. These results suggest that the erythema nodosum leprosum episode (ENL) is related to an excessive humoral response and immunoregulatory alterations.