Lettuce (Lactuca sativa) is the major leafy vegetable that is susceptible to powdery mildew disease under greenhouse and field conditions. Quantitative trait loci (QTLs) for resistance to powdery mildew under greenhouse conditions were mapped in an interspecific population derived from a cross between susceptible L. sativa cultivar Salinas and the highly susceptible L. serriola accession UC96US23. Four significant QTLs were detected on linkage groups LG 1 (pm-1.1), LG 2 (pm-2.1 and pm-2.2) and LG 7 (pm-7.1), each explaining between 35 to 42% of the phenotypic variation. The four QTLs are not located in the documented hotspots of lettuce resistance genes. Alleles for the disease resistance at the four QTLs originated from both parents (two from each), demonstrating that even highly susceptible accessions may provide alleles for resistance to powdery mildew. These QTLs appeared to operate during limited periods of time. Results of the field trials with F2:3 and F3:4 families derived from a Soraya (moderately resistant) × Salinas cross demonstrated effective transfer of resistance to powdery mildew in this material. An integrated rating approach was used to estimate relative levels of resistance in 80 cultivars and accessions tested in a total of 23 field and greenhouse experiments. Generally, very low resistance was observed in crisphead-type lettuces, while the highest relative resistance was recorded in leaf and butterhead types. Comparison of two disease assessment methods (percentage rating and the area under the disease progress steps, AUDPS) for detection of QTLs shows that the two approaches complement each other.