A generic method for the design of reactors with optimal temperature profiles has been developed. This paper focuses on the use of side-streams and inert pellets to control the temperature profiles in addition to external cooling. These two aspects of reactor design have so far been developed separately and mainly applied to laboratory-scale reaction systems. In this work, a reactor design procedure is developed that considers the combination of these two aspects simultaneously. Nitrobenzene hydrogenation and ethylene oxidation in non-isothermal and non-adiabatic reactors are used as case studies. The results show that higher reactor performance, characterised by conversion, yield or selectivity, can be achieved with optimal temperature profiles manipulated by side-streams and inert pellets. Temperature can be effectively controlled to be below a certain maximum point that causes hot spots, or thermal run-away behaviour. Various reactor designs such as Packed-Bed Membrane Reactor (PBMR), Multi-Bed Multi-Tubular Reactor (MBMTR) with side-stream injection are considered and compared with typical fixed-bed reactors. Pseudo-homogeneous (1D) and heterogeneous (1D) reactor models are used for the modelling of the reactor with SQP (Successive Quadratic Programming) and stochastic methods applied for the optimisation. (C) 2004 Elsevier Ltd. All rights reserved.