A range of approaches for QTL analysis was used to identify, characterize and dissect loci conditioning quantitative disease resistance (disease QTL) in maize. By investigating the introgression lines derived from B73 x Tx303, several QTL for resistance to northern leaf blight (NLB) were mapped. Two QTL, Tx303 allele at bin 1.06 (designated qNLB1.06Tx303) and B73 allele at bin 1.02 (designated qNLB1.02B73), were characterized in derived near-isogenic lines (NILs) using a series of macroscopic and microscopic disease components targeting different stages of NLB development pathogenesis. qNLB1.06Tx303 was found to be effective mainly against fungal penetration, and qNLB1.02B73 was effective for reducing the induction of defensive materials surrounding the infection sites, as well as inhibiting hyphal growth into the vascular bundle. Heterogeneous inbred family (HIF) analysis was explored for Two tropical lines, CML52 and targeted QTL mapping and NIL development. DK888, were chosen as donors of alleles based on their superior resistance to multiple diseases. Starting with near-inbred lines derived from B73 x CML52 and S11 x DK888, 73 SSR markers covering 39 bins were used to generate a series of NIL pairs contrasting for chromosomal regions associated with clusters of previously identified QTL for different diseases. By systemically characterizing the NIL pairs for resistance to eight diverse diseases, four disease-specific QTL, a QTL for resistance to NLB and Stewart’s wilt, and a QTL for resistance to NLB and anthracnose stalk rot, iii were identified. QTL discovered using CML52 HIFs largely conformed to the QTL mapped in a population of recombinant inbred lines (RILs) from the cross of B73 x CML52. A large-effect NLB-specific QTL at bin 8.06 (designated qNLB8.06DK888) was characterized for race specificity and allelism with two known major genes in the same region. qNLB8.06DK888 conferred race-specific resistance, and is identical, allelic, or closely linked and functionally related to Ht2. Using high-resolution breakpoint analysis, qNLB8.06DK888 was delimited to a region of ~0.46 Mb spanning from 143.92-144.38 Mb on the B73 physical map. Out of 12 annotated genes in the region, three candidate genes including two encoding protein kinases and one encoding a protein phosphatase were identified. iv