Bioinformatics contributions to microarray experiments have provided either probe designs or complex suites of analysis tools for the final data, but these efforts have not been tied together systematically such that the probe designers are required to face the performance of the probes and understand the factors that lead such outcomes to be 'noisy', or semi-quantitative. The Gibas-Weller groups have been funded by the NIH to undertake a systematic study of the factors that lead to misinterpretation of signal, and to build information systems that incorporate those factors and lead to a more quantitative, reliable outcome. The ways in which probe and target length contribute to the complexity of the interactions that must be considered will be defined. Then, the impact of cross-hybridization, secondary structure and the kinetics of the competing reactions that these represent will be discussed. Results will be presented indicating the importance of these factors and the current state of the modeling of those factors.