Antisense RNA was first an in vitro curiosity that was found to shut off protein synthesis in cell-free extracts. It was later shown to function in prokaryotic cells as a natural modulator of the synthesis of some proteins. Artificial antisense constructs can inhibit protein synthesis in prokaryotic and eukaryotic cells. To inhibit synthesis of proteins effectively, high ratios of antisense to sense RNAs are required. Thus, the challenge is to develop strategies to locate suitable targets and provide for amplification of the antisense RNA. This report provides a summary of our original work on antisense RNA.