In this prospective, randomized study, two regimens of total intravenous anaesthesia (TIVA), with propofol and S(+)-ketamine (S-ketamine) and with propofol and alfentanil, were compared with reference to endocrine stress response, circulatory effects and recovery. METHODS. The investigation was conducted in two groups of 20 ASA I-III patients over 60 years of age who were scheduled for endoprothetic orthopaedic surgery. After oral premedication with midazolam, patients received a TIVA with body-weight-adjusted doses of propofol, and S-ketamine or alfentanil as the analgesic component. For CPPV (PEEP 5 mbar), air and oxygen (FiO2 33%) were used. For muscle relaxation, patients of both groups received vecuronium in body-weight-adjusted doses. Blood samples were taken through a central venous line at seven time points before induction of anaesthesia and on the first morning after the operation also for analysis of epinephrine, norepinephrine (by HPLC/ECD), and ADH, ACTH and cortisol (by RIA). In addition, SAP, HR, arterial oxygen saturation, recovery from anaesthesia and side effects were observed. RESULTS. The two groups had comparable group mean values for age (S-ketamine group 71 years, alfentanil-group 70 years), other biometric data, and duration of anaesthesia and operation (Table 1). Plasma levels of epinephrine, norepinephrine (Table 2, Fig. 1), ADH (Table 2, Fig. 2) ACTH and cortisol (Table 2, Fig. 3) were higher in the S-ketamine-group (P < 0.05) owing to the intraoperative course of these endocrine parameters. Before induction, and on the first morning after the operation, levels were comparable between the groups. 5 min after the induction of anaesthesia, SAP and HR (Table 3) were significantly lower in the alfentanilgroup (P = 0.001). Recovery from anaesthesia (orientation with respect to person and location) was faster in the alfentanilgroup (16 vs 39 min, P = 0.001). An arterial oxygen saturation below 90% was observed in 7 patients in the S-ketamine- and 13 patients in the alfentanilgroup (P = 0.03). Four patients with S-ketamine reported dreams, and 1 dream was judged negative. Postoperative emesis was found in 6 patients in the S-ketaminegroup and 12 patients in the alfentanilgroup (P = 0.03). All patients said they would agree to undergo the same anaesthetic technique again. CONCLUSIONS. Considerable differences were found in the endocrine stress response of the two groups. With respect to endocrine response and circulation, TIVA with propofol and S-ketamine had sympathomimetic properties with positive circulatory effects and led to moderate endocrine stimulation. This should be kept in mind in patients with hypotension, hypothyrosis, or adrenocortical insufficiency; because "eustress" might be beneficial in this group of patients. On the other hand, TIVA with propofol and alfentanil showed sympatholytic properties, with negative circulatory effects and a remarkable reduction of endocrine stress response. This might be beneficial in patients with hypertension and states of endocrine hyperfunction. Both regimens were accompanied by such typical side effects as dreams, delayed recovery, reduced ventilation, and emesis, which should also be considered.