Previous studies on reactor-separator networks have focused largely on first- and second-order kinetics. A study of the effect of autocatalytic kinetics has been restricted to cases where the separator is a single-stage process. In this work, the effect of autocatalytic kinetics on the design and operation of a reactor-separator system, where the separator is a multistage distillation column, is investigated. Apart from steady-state design and stability, dynamic aspects such as response to disturbances and set-point changes are studied in detail. It was found that when the reactor holdup is maintained constant, for stable operation, the exit reactor concentration (mole fraction of the reactant A) has to be <1/2 for quadratic autocatalysis and <1/3 for cubic autocatalysis. Further, in the stable regime, the ability of the system to absorb changes in the inlet flow rate or the composition decreases as the domain of instability is approached. Regarding dynamics, we observe that the response of the system becomes slower with an increase in the base steady-state value of the exit reactor composition in the stable regime. This is correlated with the appropriate time constant, which shows a qualitatively different behavior for autocatalytic kinetics as compared to first-order or second-order kinetics. Snowball effects, which refer to sharp changes in the distillate rate due to small changes in the inlet flow rate, were also found to be dominant. For the case of variable reactor holdup, the range of stable operation is increased for quadratic autocatalysis. In general, settling times are larger when compared to the case of constant holdup, but the percentage deviations from steady-state values due to changes in the inlet flow rate and the composition are smaller. Further, snowball effects are negligible. © 2005 American Chemical Society.