The immature and mature heart differs from each other in terms of its excitability, action potential properties, contractility and relaxation. This includes upregulation of repolarizing K⁺ currents, an enhanced inward rectifier K⁺ current and changes in Ca²⁺, Na⁺ and Cl^- currents. At the molecular level, the developmental regulation of ion channels is scantily described. Using a large-scale real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay, we performed a comprehensive analysis of ion channel transcript expression during perinatal development in the embryonic (E17.5), neonatal (P1-2) and adult Swiss-Webster mouse hearts. These data are compared with publicly available microarray data sets (Cardiogenomics project). Developmental mRNA expression for several transcripts was consistent with the published literature. For example, transcripts such as Kir2.1, Kir3.1, Nav1.5, Cav1.2, etc were upregulated after birth, whereas others (e.g. KCa2.3 and minK) were downregulated. Cl- channel transcripts were expressed at higher levels in immature heart; particularly those that are activated by intracellular Ca²⁺. Defining alterations in the ion channel transcriptome during perinatal development will lead to a much improved understanding of the electrophysiological alterations occurring in the heart after birth. Our study may have important repercussions in understanding the mechanisms and consequences of electrophysiological alterations in infants and may pave the way for better understanding of clinically relevant events such as congenital abnormalities, cardiomyopathies, heart failure, arrhythmias, cardiac drug therapy and the sudden infant death syndrome.