The possible use of <sup>14</sup>CO measurements to constrain hydroxyl radical (OH) concentrations in the atmosphere is investigated. <sup>14</sup>CO is mainly produced in the upper atmosphere from cosmic radiation. Measurements of <sup>14</sup>CO at the surface show lower concentrations compared to the upper atmospheric source region, which is the result of oxidation by OH. In this paper, the sensitivity of <sup>14</sup>CO mixing ratio surface measurements to the 3-D OH distribution is assessed with the TM5 model. Simulated <sup>14</sup>CO mixing ratios agree within a few molecules <sup>14</sup>CO cm<sup>−3</sup> (STP) with existing measurements at five locations worldwide. The simulated cosmogenic <sup>14</sup>CO distribution appears mainly sensitive to the assumed upper atmospheric <sup>14</sup>C source function, and to a lesser extend to model resolution. As a next step, the sensitivity of <sup>14</sup>CO measurements to OH is calculated with the adjoint TM5 model. The results indicate that <sup>14</sup>CO measurements taken in the tropics are sensitive to OH in a spatially confined region that varies strongly over time due to meteorological variability. Given measurements with an accuracy of 0.5 molecules <sup>14</sup>CO cm<sup>−3</sup> STP, a good characterization of the cosmogenic <sup>14</sup>CO fraction, and assuming perfect transport modeling, a single <sup>14</sup>CO measurement may constrain OH to 0.2–0.3×10<sup>6</sup> molecules OH cm<sup>−3</sup> on time scales of 6 months and spatial scales of 70×70 degrees (latitude×longitude) between the surface and 500 hPa. The sensitivity of <sup>14</sup>CO measurements to high latitude OH is about a factor of five higher. This is in contrast with methyl chloroform (MCF) measurements, which show the highest sensitivity to tropical OH, mainly due to the temperature dependent rate constant of the MCF–OH reaction. A logical next step will be the analysis of existing <sup>14</sup>CO measurements in an inverse modeling framework. This paper presents the required mathematical framework for such an analysis.