Although heterosis has been exploited commercially for close to a century, the molecular mechanisms underlying hybrid vigor are not well understood. Multiple models, including dominance and complementation, have been proposed. Maize inbred lines B73 and Mo17 produce hybrids that exhibit heterosis and are a model system for heterosis. Historically, quantitative genetic approaches have been utilized to understand the regulation of heterosis as it affects traits such as yield. Recent technological advances have allowed for global studies of gene expression in inbreds and hybrids. Multiple modes of gene action detected in a microarray comparison of B73, Mo17, and their Mo17xB73 hybrid are consistent with multiple molecular mechanisms contributing to heterosis. The reciprocal hybrids generated by crossing B73 and Mo17 differ phenotypically from each other despite having identical nuclear genomes. Microarray comparisons of the reciprocal hybrids reveal substantial differences in gene expression in vegetative seedlings, suggesting that parent-of-origin effects on expression may contribute to the phenotypic differences observed throughout development. To better understand the regulation of gene expression, eQTL microarray studies were conducted using the IBM RILs and their hybrids generated by crossing the RILs with B73 and Mo17. A predominance of trans-eQTL (~80%) are detected and exhibit non-additive expression patterns consistent with paternal-eQTL regulation of gene expression in hybrids. Together, these studies provide a comprehensive understanding of gene expression patterns and regulation of gene expression between inbred and hybrid lines and support the involvement of complex regulatory mechanisms such as imprinting and small RNAs in heterosis.