Genome-wide ChIP-chip assays of protein-DNA interactions yield large volumes of data requiring effective statistical analysis to obtain reliable results. Successful analysis methods need to be tailored to platform specific characteristics such as probe density, genome coverage, and the nature of the controls. We describe the use of the respective software packages MAT and MA2C for the analysis of ChIP-chip data from one-color Affymetrix and two-color NimbleGen or Agilent tiling microarrays.