Microdialysis was used in the freely moving rat to measure the effects of graded changes in brain glucose on the serotonergic and noradrenergic projections to the hippocampus. The concentration of glucose in the dialysate was monitored using an enzyme-based assay. A systemic injection of insulin caused a steep decline in glucose level which was restored to the control level by oral administration of glucose solution. The changes in 5-hydroxytryptamine (5-HT) and noradrenaline were a mirror image of the glucose changes: they rose after insulin injection and returned to control during glucose administration. A delayed increase was shown by 5-hydroxyindoleacetic acid (5-HIAA) which did not return to baseline on glucose administration. The metabolite dihydroxyphenylacetic acid (DOPAC) decreased after insulin administration and increased above control during glucose administration. While the responses of 5-HT, noradrenaline and 5-HIAA to hypoglycaemia resemble those to mild stress, the changes in DOPAC are the reverse of those produced by stress.