Genetic variation influences gene expression, and this can be efficiently mapped to specific genomic regions and variants. We used gene expression profiling of EBV-transformed lymphoblastoid cell lines of all 270 individuals of the HapMap consortium to elucidate the detailed features of genetic variation underlying gene expression variation. We find gene expression levels to be heritable and differentiation between populations in agreement with earlier small-scale studies. A detailed association analysis of over 2.2 million common SNPs per population (5% frequency HapMap) with gene expression identified at least 1348 genes with association signals in cis and at least 180 in trans. Replication in at least one independent population was achieved for 37% of cis- signals and 15% of trans- signals, respectively. Our results strongly support an abundance of cis- regulatory variation in the human genome. Detection of trans- effects is limited but suggests that regulatory variation may be the key primary effect contributing to phenotypic variation in humans. Finally, we explore a variety of methodologies that improve the current state of analysis of gene expression variation.