An epidemiologic survey (n = 466) was conducted in an area of subtropical rainforest in north-west Ecuador with the following objectives: (1) to determine the prevalence of cutaneous leishmaniasis (CL), (2) to identify the Leishmania species causing human disease, (3) to investigate the major clinical manifestations of leishmaniasis, (4) to study cellular and humoral immune response indicators associated with disease status and (5) to identify risk factors for CL. Fourteen percent of subjects had parasitologically confirmed CL; 33% had evidence of prior disease. However, 17.2% of subjects with a negative CL clinical history presented with a positive Montenegro skin test (MST), indicating the possibility of subclinical infection. The species isolated from subject lesions were L. guyanensis (63%), L. panamensis (33%), and L. brazilensis (4%). Mean specific anti-Leishmania IgG and IgM OD serum levels were highest in subjects diagnosed with current CL, followed by those with prior CL, and were lowest in healthy subjects, respectively (0.56 +/- 0.27 vs 0.33 +/- 0.2 vs 0.22 +/- 0.14; F-ratio = 74; P < 0.00001) and (665 +/- 270 vs 481 +/- 220 vs 301 +/- 128.5; F-ratio = 37; P < 0.00001). Likewise, subjects with present CL had measurably higher MST reactions (13 +/- 6.7 mm) than those with prior CL (10.9 +/- 7.8 mm) or healthy individuals (2.4 +/- 2.5 mm; F-ratio = 106; P < 0.00001). Serum concentrations of IgG were predicted by lesion number (t = 2.5; P = 0.018), size (t = 3.7; P = 0.0006), and duration (t = 3.5; P = 0.0013). Furthermore, the MST induration size increased as a function of lesion number (t = 3.0; P = 0.005) and size (t = 3.4; P = 0.022). Subject age and sex did not predict serum IgG or IgM concentrations or MST reactions in the 3 disease groups. Although no sex differences were found with respect to clinical characteristics, children < or = 12 years of age were almost 3 times more likely to have CL lesions or scars located on the face and head area compared to adults (OR = 2.75; 95% CI = 1.4-5.6, P = 0.004). The risk factors associated with disease included age under 5 years (AOR = 1.5; 95% CI = 0.48-2.35), male gender in adults (AOR = 2.8; 95% CI = 1.1-7.8), and wood and/or cane exterior house walls (AOR = 1.8; 95% CI = 1.4-2.5). In contrast, electric home lighting was associated with decreased risk (AOR = 0.7; 95% CI = 0.4-2.3). The results suggest that it may be possible to modify a portion of the risk of CL by making changes in the housing environment which may help to reduce the amount of human-vector contact.