Schistosomiasis is a major public health problem in many developing countries. Previous studies have shown that infection levels by Schistosoma mansoni in a Brazilian population is controlled by a major gene, denoted as SM1, which was mapped to chromosome 5q31-q33 by use of a model-based (logarithm of the odds [lod] score) analysis method. The present study is an autosome-wide scan searching for additional human loci implicated in the regulation of S. mansoni infection intensities. The weighted pairwise correlation model-free linkage method was used in order to consider large pedigrees and to conduct a 2-locus analysis (i.e., to search for a second locus taking into account linkage to 5q31-q33). The most significant linkage results were again obtained in the 5q31-q33 region. Two additional regions provided linkage results with significance levels around 0.001, 1p21-q23 (results independent of 5q31-q33) and 6p21-q21 (results in interaction with 5q31-q33). The investigation of these regions, which contain some candidate genes, is ongoing in other populations to confirm the role of these regions.