Reactivity ratios for the important acrylamide (AAm)/acrylic acid (AAc) copolymerization system exhibit considerable scatter in previously published literature, and therefore, there is a need for more definitive values for these reactivity ratios. An appropriate methodology, based on the error-in-variables-model (EVM) framework along with a direct numerical integration procedure, is applied in order to determine reliable reactivity ratios. The reliability of the results is confirmed with extensive and independent replication. Furthermore, via an EVM-based criterion for the design of experiments using mechanistic models, optimal feed compositions are calculated, and from these optimal reactivity ratios are estimated for the first time (r(AAm) = 1.33 and r(AAc) = 0.23) based on information from the full conversion range. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4819-4827