Circulating RNA in plasma and serum is a newly developed area for molecular diagnosis. To date, increasing numbers of studies show that plasma and serum RNA could serve as both tumor- and fetal-specific markers for cancer detection and prenatal diagnosis, respectively. Recently, by introducing the highly sensitive one-step real-time quantitative reverse-transcription (RT)-polymerase chain reaction (PCR), these potentially valuable RNA species, which often only exist at low concentrations in plasma and serum, can now be readily detected and quantified. Following the successful quantification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in plasma of normal individuals, several placenta-derived mRNA species, including the mRNA transcripts of human placental lactogen (hPL), the beta-subunit of human chorionic gonadotropin (betahCG), and corticotropin-releasing hormone (CRH) were also quantified in plasma of pregnant women. These circulating placental RNA species have provided the fetal-polymorphism-independent markers for prenatal diagnosis. The achievement in detecting the placental RNA in maternal plasma represents a significant step toward the development of RNA markers for noninvasive prenatal gene expression profiling. This detection technique can be extended to access a wide range of disease conditions, such as cancer and trauma. The one-step, real-time quantitative RT-PCR is a highly sensitive and specific, yet practically simple, RNA detection technique. This powerful technology may allow the practical employment of circulating RNA in the high-throughput clinical screening and monitoring applications.