Sequence divergence scaled by variation within species has been used to infer the action of selection upon individual genes. Applying this approach to expression, we compared whole-genome whole-body RNA levels in 10 heterozygous Drosophila simulans genotypes and a pooled sample of 10 D. melanogaster lines using Affymetrix Genechip. For 972 genes expressed in D. melanogaster, the transcript level was below detection threshold in D. simulans, which may be explained either by sequence divergence between the primers on the chip and the mRNA transcripts or by down-regulation of these genes. Out of 6,707 genes that were expressed in both species, transcript level was significantly different between species for 534 genes (at P < 0.001). Genes whose expression is under stabilizing selection should exhibit reduced genetic variation within species and reduced divergence between species. Expression of genes under directional selection in D. simulans should be highly divergent from D. melanogaster, while showing low genetic variation in D. simulans. Finally, the genes with large variation within species but modest divergence between species are candidates for balancing selection. Rapidly diverging, low-polymorphism genes included those involved in reproduction (e.g., Mst 3Ba, 98Cb; Acps 26Aa, 63F; and sperm-specific dynein). Genes with high variation in transcript abundance within species included metallothionein and hairless, both hypothesized to be segregating in nature because of gene-by-environment interactions. Further, we compared expression divergence and DNA substitution rate in 195 genes. Synonymous substitution rate and expression divergences were uncorrelated, whereas there was a significant positive correlation between nonsynonymous substitution rate and expression divergence. We hypothesize that as a substantial fraction of nonsynonymous divergence has been shown to be adaptive, much of the observed expression divergence is likewise adaptive.