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Foxtail millet [Setaria italica (L.) P. Beauv.] is a largely self-pollinating species that is used as a warm-season annual in the USA. Nearly all cultivars of this species grown in the USA are selections from land races. This research was undertaken to determine whether sufficient high-parent heterosis is expressed in foxtail millet for grain yield and other key traits to justify the development and use of varietal crosses. Seven diverse parents and 21 F2s and 21 F3s produced from biparental crosses were evaluated in five environments in 1996. Genotype x environment interaction was highly significant for grain yield, but the highest yielding entries were high-yielding in each environment. High-parent heterosis for grain yield was detected in 18 of 21 F2s. On the basis of the estimate of average heterosis, which was highly significant in every environment, the expected yield of the F1 generation was 68% greater than the average yield of the parental cultivars. This high level of heterosis for grain yield suggested that varietal crosses or other types of cultivars in which there exists a relatively high amount of heterozygosity would provide a significant yield benefit over nonhybrid cultivars. Although significant heterotic effects was observed for each of the other traits, additive effects were more important. Significant correlations between traits of the estimates of additive and/or variety heterosis effects suggest that at least some of the genes controlling grain yield, plant height, and spike length were either the same or in coupling phase linkage.