A study of leishmanin skin test reactors was carried out in 1997 and 1998 in an endemic region in southeast Spain, to estimate the magnitude of and the factors related to subclinical Leishmania infantum infection. In the main focus of leishmaniasis in the region, 11.5% of the children and 52.8% of the adults reacted to the skin test. Among the adults, the response was significantly greater for males and for those who had resided in the area for > or = 15 years. In the whole region, 3.7% 14-year-old students reacted to the skin test, with no gender differences. The main factors related to a positive skin test result were having a parent or sibling recovered from leishmaniasis (relative risk = 14) and living in the rural periphery of the region as opposed to the metropolitan area (relative risk = 4). These results indicate a high frequency of subclinical leishmaniasis in the region. We postulate that the decline in childhood visceral leishmaniasis in southern Europe in the second half of the 20th century is related to social changes, which gave rise to a less frequent exposure at a young age as well as a lowered susceptibility to disease through nutritional and immune improvements.