The objective of the present study was to identify quantitative trait loci (QTL) influencing agronomic performance across rain fed Mediterranean environments in a recombinant inbred line (RIL) population derived from the barley cultivars ER/Apm and Tadmor. The population was tested in four locations (two in Syria and two in Lebanon) during four consecutive years. This allowed the analysis of marker main effects as well as of marker by location and marker by year within location interactions. The analysis demonstrated the significance of crossover interactions in environments with large differences between locations and between years within locations. Alleles from the parent with the higher yield potential, ER/Apm, were associated with improved performance at all markers exhibiting main effects for grain yield. The coincidence of main effect QTL for plant height and yield indicated that average yield was mainly determined by plant height, where Tadmor???s taller plants, being susceptible to lodging, yielded less. However, a number of crossover interactions were detected, in particular for yield, where the Tadmor allele improved yield in the locations with more severe drought stress. The marker with the highest number of cross-over interactions for yield and yield component traits mapped close to the flowering gene Ppd-H2 and a candidate gene for drought tolerance HVA1 on chromosome 1H. Effects of these candidate genes and QTL may be involved in adaptation to severe drought as frequently occurring in the driest regions in the Mediterranean countries. Identification of QTL and genes affecting field performance of barley under drought stress is a first step towards the understanding of the genetics behind drought tolerance.