We have studied the effect of 1 or 2 MAC isoflurane with or without ketanserin on cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2) and CBF autoregulation in 20 adult patients undergoing lumbar disc surgery. Ten patients received ketanserin and 10 isotonic saline. CBF measurements were started after 1 h of infusion of saline or ketanserin. The patients were anaesthetized with thiopentone 5 mg kg-1 followed by isoflurane. During 1 MAC of isoflurane, baseline values were recorded and then CBF autoregulation was examined (mean arterial pressure increased by about 30% with angiotensin). The sequence was repeated with 2 MAC of isoflurane. CBF was measured by the i.v. xenon-133 technique. CMRO2 was calculated as the product of CBF and the cerebral arterio-venous oxygen content difference. Ketanserin had no effect on CBF, CMRO2 or CBF autoregulation during isoflurane anaesthesia, therefore all patients were pooled for evaluation of the effect of isoflurane. Increasing isoflurane anaesthesia from 1 to 2 MAC increased mean CBF from 41 to 49 ml/100 g min-1 (P < 0.01) and decreased mean CMRO2 from 1.5 to 1.1 ml/100 g min-1 (P < 0.001) and thus abolished the coupling between flow and metabolism. The CBF autoregulation test indicated that autoregulation was disrupted at 2 MAC, but not during 1 MAC isoflurane anaesthesia.