We studied the clinical use of an automatic feedback control system to adjust the end-tidal anaesthetic concentration with a low-flow method. The end-tidal controller uses two input signals (the end-tidal and inspiratory concentrations) to control the isoflurane concentration in the fresh gas flow, using a model-based algorithm. We studied 22 ASA I-III patients during elective surgery lasting more than 2 h. The anaesthetist was asked to make four step changes of the target end-tidal concentration (+0.3, +0.6, -0.3, -0.6 vol%), either manually (Group A) or by setting the target value for the feedback controller (Group B), and then the control was changed and the step changes were repeated, in a crossover design. Eighty step changes with each control method were compared in terms of response time, maximal overshoot and stability. The automatic control system was more accurate and stable than the human controller for step increases and step decreases, with less overshoot/undershoot and greater stability [e.g. maximal overshoot 14.7 (SD 3.7)% and 18 (8.1)% respectively for +0.6 vol% step changes, and 19.8 (3.7)% and 30.7 (13.2)% respectively for +0.3 vol% step changes]. However, the automatic control system showed a faster response time than the manual method only with large increasing steps (e.g. 149 (32) s and 205 (57) s respectively for +0.6 vol% step changes) and was not different from manual control for decreasing steps. Automatic control of the end-tidal isoflurane concentration can be better than human control in a clinical setting, and this task could be done automatically.