We evaluated the hypothesis that the Drosophila melanogaster second chromosome gene scabrous (sca), a candidate sensory bristle number quantitative trait locus (QTL), contributes to naturally occurring variation in bristle number. Variation in abdominal and sternopleural bristle number was quantified for wild-derived sca alleles in seven genetic backgrounds: as homozygous second chromosomes (C2) in an isogenic background, homozygous lines in which approximately 20 cM including the sca locus had been introgressed into the isogenic background (sca BC), as C2 and sca BC heterozygotes and hemizygotes against a P element insertional sca allele and a P-induced sca deficiency in the same isogenic background, and as sca BC heterozygotes against the wild-type sca allele of isogenic strain. Molecular restriction map variation was determined for a 45 kb region including the sca locus, and single-stranded conformational polymorphism (SSCP) was examined for the third intron and parts of the third and fourth exons. Associations between each of the 27 molecular polymorphisms and bristle number were evaluated within each genotype and on the first principal component score determined from all seven genotypes, separately for each sex and bristle trait. Permutation tests were used to assess the empirical significance thresholds, accounting for multiple, correlated tests, and correlated markers. Three sites in regulatory regions were associated with female-specific variation in abdominal bristle number, one of which was an SSCP site in the region of the gene associated with regulation of sca in embryonic abdominal segments.