Dosage compensation, the equalized X chromosome gene expression between males and females in Drosophila, has also been found in triple X metafemales. Inverse dosage effects, produced by genomic imbalance, are believed to account for this modulated expression, but they have not been studied on a global level. Here, we show a global expression comparison of metafemales (XXX; AA) with normal females (XX; AA) with high-throughput RNA-sequencing. We found that the majority of the X-linked genes in metafemales exhibit dosage compensation with an expression level similar to that of normal diploid females. In parallel, most of the autosomal genes were expressed at about two-thirds the level of normal females, the ratio of inverse dosage effects produced by the extra X chromosome. Both compensation and inverse effects were further confirmed by combination of X-linked and autosomally located miniwhite reporter genes in metafemales and relative quantitative PCR of selected genes. These data provide evidence for an inverse dosage component to X chromosome compensation.