The effect of imipramine on symptomatic peripheral diabetic neuropathy in 9 patients was examined in a double-blind cross-over study against placebo. The dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 300-750 nM. Imipramine had a clear beneificial effect on the symptoms of the neuropathy, whereas no changes in a range of neurophysiological measurement was detected. Despite some adverse effects, especially of an anticholinergic nature, the patients generally preferred imipramine to placebo.