The regulatory mechanisms underlying myometrial smooth muscle contractility during labor are poorly understood. The authors therefore investigated the transcriptional profile of the charges that occur in the human myometrium at term pregnancy when compared with that at labor. Microarray technology was used to identify differentially expressed genes in human myometrium at labor. Real-time fluorescence reverse-transcriptase polymerase chain reaction (RT-PCR) was subsequently performed to verify the microarray data. Semiquantitative RT-PCR, Western blotting, and microscopy methodologies were also used. Certain novel genes were found to be upregulated in human myometrium at labor. Of these, PSCDBP, TLR2, TWIST1, FLJ35382, and RGS12 have not been previously characterized or identified in human myometrium. EDNRB is the other novel labor-associated gene whose reported expression is also upregulated at labor. All 6 genes were expressed on human myometrial smooth muscle cells. These novel upregulated genes are involved in multiple pathways that may be associated with a variety of cellular processes including inflammation, transcriptional regulation, and intracellular signaling.