A new self-tuning controller (STC) has been developed for a general class of nonlinear multiinput, multioutput process models. These models can include arbitrary, known nonlinear functions of the old inputs and outputs as well as the products of these functions and any powers of the most recent inputs. A very general control algorithm has been proposed that allows different numbers of inputs and outputs, different time delays for each input-output pair, and a performance index that can include different penalties on the outputs and on the incremental changes in the outputs. Simulation results are presented for two-point composition control of a pilot-scale distillation column. The results demonstrate that the new nonlinear STC performs significantly better than conventional STC's based on linear models.