Drought is a major constraint to rice (Oryza sativa L.) production in rainfed and poorly irrigated environments. Identifying genomic regions influencing the response of yield and its components to water deficits will aid our understanding of the genetic mechanism of drought tolerance (DT) of rice and the development of DT varieties. Grain yield (GY) and its components of a recombinant inbred population developed from a lowland rice and an upland rice were investigated under different water levels in 2003 and 2004 in a rainout DT screening facility. Correlation and path analysis indicated that spikelet fertility (SF) was particularly important for grain yield with direct effect (P=0.60) under drought stress, while spikelet number per panicle (SN) contributed the most to grain yield (P=0.41) under well-watered condition. A total of 32 quantitative trait loci (QTLs) for grain yield and its components were identified. The phenotypic variation explained by individual QTLs varied from 1.29% to 14.76%. Several main effect QTLs affecting SF, 1,000-grain weight (TGW), panicle number (PN), and SN were mapped to the same regions on chromosome 4 and 8. These QTLs were detected consistently across 2 years and under both water levels in this study. Several digenic interactions among yield components were also detected. The identification of genomic regions associated with GY and its components under stress will be useful to improve drought tolerance of rice by marker-aided approaches.