Reactive distillation (RD), an unconventional and attractive technique, has been applied in fuel ether production. A typical application of RD is the synthesis of the widely used methyl tert-butyl ether (MTBE). RD has also been found to have potential to produce high quality ethyl tert-butyl ether (ETBE), a potential alternative to MTBE. A RD process integrates conventional reaction and separation into a single unit, resulting in extra complexity and dual process objectives, i.e. maximization of reactant conversion and purity of products. The conversion and the purity are thus important variables to be controlled in RD of ETBE. Unfortunately, both of them are not economically and reliably available for closed-loop control. This study aims to develop an effective method to infer the conversion and the purity from multiple temperature measurements that are easily available on-line and in real time. Nonlinear inferential models are recommended for ETBE synthesis with a ten-stage pilot scale RD column. The models are two-variable third-order regressive models, in which the temperature measurements of the reboiler and the bottom reactive section are employed. Experimental design, model identification, and model testing are also investigated.