Egypt has the world's highest rice productivity from unit area, yet yield was constrained by biotic stresses being targeted by breeders. This work was carried out at the experimental Farm of Rice Research and Training Center, Sakha Kafer El-Sheik, Egypt, during 2011 and 2012 rice growing seasons. Five parents and their 10 hybrids were used to study gene action, combining ability and heterosis for certain agronomic traits and biotic stresses. Giza177 and M101 rice varieties were resistant to rice blast, while GZ6214 and M202 were resistant to stem borer, and both M201 and M202 to white tip nematode. General combining ability (GCA) and specific combining ability (SCA) were highly significant for all studied traits. M202 gave highly significant and negative estimates of GCA effects desired for plant height, vegetative stage, reproductive stage and days to heading. Significant and highly significant negative estimates of SCA effects were found for plant height, vegetative stage and days to heading. The best crosses for yield and its components were Giza177 x GZ6214, Giza177 x M201, Giza177 x M202, GZ6214 x M201 and GZ6214 x M202. Regarding stem borer infestation, the crosses M101 x M201, M101 x M202 and Giza177 x GZ6214 gave highly significant and desirable negative estimates of SCA. For blast reaction, stem borer infestation and white tip nematode two hybrid combinations, Giza177 x GZ6214 and GZ6214 x M201 recorded highly significant negative desirable heterosis and showed highly significant negative SCA effects. M202 was a good resource for resistance to white tip nematode, with all crosses with this cultivar having low levels of infection. Principal component analysis as one of Multivariate analysis components was used to study the genetic dissimilarity and relative importance of agronomic and biotic traits as a source of variation among the five parents and their hybrids. The first three principal components were significant and accounted about 80.4 % of the total variance of all characters. The 15 rice genotypes were grouped into three major clusters based on relative dissimilarity among them with significant differences among these groups for most characters, the progeny produced from crossing between Egyptian and US parents which are distantly related showed divergent distance and gave values surpassed their parents in most characters. The results of all multivariate analysis showed that US parent M202 is the most divergent parent. Grain yield plant^-1, filled grains panicle^-1and blast reaction were the most important source of variation among all genotypes with largest coefficients on the first PC axis. However, the second axis PC2 deals with the most earliness characters; vegetative stage and days to heading. On the other side, PC3 was dominated by white tip nematode. Finally, crossing among more genetic divergent Egyptian rice varieties Giza 177, GZ6214 and US parents created new suitable combinations in breeding program. Rice breeder can maximize genetic diversity among new cultivars, meanwhile at the same time maintaining the level of desired agronomic traits present in current popular cultivars.