The effect of the selective serotonin reuptake inhibitor citalopram on diabetic neuropathy symptoms was examined in a double-blind, placebo-controlled, crossover study for two 3-week periods. Citalopram was given as a fixed dose of 40 mg/day. Data from 15 patients could be included in the statistical analysis. Citalopram significantly relieved the symptoms of neuropathy as measured by both observer- and self-rating in comparison with placebo. The steady-state plasma concentration of citalopram was 10 to 890 nmol/L. There was no significant relationship between the plasma concentration of citalopram and the effect of treatment as measured by observer- or self-rating. Two of 17 patients, both receiving citalopram, left the study because of side effects (nausea and vomiting or gastric upset and diarrhea). Side-effect ratings were significantly higher during administration of citalopram than during administration of placebo, but citalopram was generally well tolerated. Compared with earlier results obtained with imipramine administered on the basis of plasma level monitoring, citalopram appeared to be less effective, but seemed to be better tolerated.