To begin to understand the genetic architecture of natural variation in gene expression, we carried out genetic linkage analysis of genomewide expression patterns in a cross between a laboratory strain and a wild strain of Saccharomyces cerevisiae. Over 1500 genes were differentially expressed between the parent strains. Expression levels of 570 genes were linked to one or more different loci, with most expression levels showing complex inheritance patterns. The loci detected by linkage fell largely into two categories: cis-acting modulators of single genes and trans-acting modulators of many genes. We found eight such trans-acting loci, each affecting the expression of a group of 7 to 94 genes of related function.