In higher eukaryotes, E2F transcription factors often drive expression of genes necessary for the cell cycle, notably the G1/S phase transition. With conventional transcriptional reporter systems, expression of a reporter gene from an E2F-responsive promoter would allow one to identify the fraction of cells making this transition. Here, we have engineered an E2F-responsive genetic reporter system that outputs the proliferation rate. The system takes advantage of the long half-lives of fluorescent protein reporters and output signal normalization. By doing so, it converts dynamic pulses of E2F activity into an analog output proportional to the proliferation rate. Such a system should be useful for applications involving high-throughput drug or genetic screens, investigation of cellular environment, and biological engineering. Biotechnol. Bioeng. 2011; 108: 2003-2010. (C) 2011 Wiley Periodicals, Inc.