We have studied the development of tolerance to the anaesthetic effects of propofol in rats. In the first set of experiments, three groups of rats (A, B and C) received i.v. propofol 10 mg kg−1, 15 mg kg−1 and 20 mg kg−1, respectively. The durations of anaesthesia were recorded, the rats were killed and blood was collected to measure the concentrations of propofol. In a second set of experiments, rats received propofol 10 mg kg−1 i.v. repeated 24 h (group D), 48 h (group E) or 72 h (group F) later. Sleeping times were recorded after the first and the second administration and concentrations of propofol at awakening were measured after the second dose, when rats were killed. Sleeping times were significantly longer in groups B (22.4 min) and C (25.9 min) compared with group A (13.7 min) (P < 0.001 for both). Durations of anaesthesia in groups D, E and F were 14.7, 14.5 and 14.3 min, respectively, after the first dose of propofol and 11.6, 12.1, and 14.9 min, respectively, after the second dose. The rats in groups D and E exhibited shorter sleeping times after the second dose of propofol than after the first (P < 0.01 for both). Concentrations of propofol at awakening did not differ between groups A, B and C or between groups D, E and F. The results suggest lack of changes in susceptibility of the CNS to the anaesthetic effects of propofol. (Br. J. Anaesth. 1994; 72: 127–128)