Using microdialysis, we have examined the effects of ketamine on concentrations of total nitric oxide oxidation products (NOx-) in the rat hippocampus and striatum in vivo to investigate the relationship between anaesthesia and NOx- production in the brain. Ketamine 25, 50 and 100 mg kg(-1) i.p. increased NOx- concentrations to mean 125 (SD 13)%, 165 (11)% and 193 (13)% of basal, respectively, in the hippocampus and to 122 (12)%, 147 (7)% and 177 (14)% of basal in the striatum. Local perfusion with ketamine 50 and 100 mu mol litre(-1) into the hippocampus or striatum increased NOx- concentrations to 212 (32)% and 291 (17)% of basal, respectively, in the hippocampus and to 148 (20)% and 201 (18)% of basal in the striatum. Ketamine 50 and 100 mg kg(-1) i.p. caused dose-dependent prolongation of loss of the righting reflex (LRR) and 100 mg kg(-1) i.p. also caused loss of the corneal reflex (LCR). Local perfusion of ketamine did not provoke LRR or LCR. Inhibition of NOS by L-NAME 100 mg kg(-1) i.p. decreased hippocampal NOx- concentrations to 58 (7)% of basal and did not provoke LRR or LCR. Although the effect of ketamine-induced increases in hippocampal NOx- concentrations was significantly depressed by L-NAME, LRR was not affected. These data imply that NOx-concentrations in the hippocampus or striatum have no direct relationship to the anaesthetic efficacy of ketamine, although this requires further investigation.