We provide experimentally based topology models for 37 integral membrane proteins from Saccharomyces cerevisiae. A C-terminal fusion to a dual Suc2/His4C topology reporter has been used to determine the location of the C terminus of each protein relative to the endoplasmic reticulum membrane, and this information is used in conjunction with theoretical topology prediction methods to arrive at a final topology model. We propose that this approach may be used to produce reliable topology models on a proteome-wide scale.