BACKGROUND Atopic dermatitis (AD) can be aggravated by mental stress. We recently showed that pretreatment with tandospirone citrate (TC), a serotonin (5-HT) agonist for the 5-HT(1A) receptor subtype, significantly inhibits stress-induced degranulation of mouse dermal mast cells. OBJECTIVE To evaluate the efficacy of TC in treatment of AD. METHODS Changes in anxiety levels, depression symptoms and the clinical severity of AD after administration of TC were examined. Data were collected for 20 patients with AD who received TC 30 mg/day for 4 weeks and 17 patients with AD who did not receive the drug. Profile of Mood States (POMS) scores were used to measure several types of mental stress. Severity of AD was evaluated using the SCORAD Index, and the patients' level of stress and sleeping status were evaluated using visual analogue scales. RESULTS Before TC administration, all scores were markedly different in the 37 patients compared with 37 normal healthy controls matched for age and gender. POMS scores for tension-anxiety (T-A) and the SCORAD Index decreased significantly in patients who received TC, but did not change significantly in the untreated patients. The two groups had significantly different treatment responses based on changes in T-A scores. There was a significant correlation between changes in the T-A score and SCORAD Index. CONCLUSIONS These data suggest that anxiolytic drugs such as 5-HT(1A) agonists are useful in the clinical management of stress-associated aggravation of AD. Inhibition of stress-induced mast cell degranulation may be one of the mechanisms underlying the clinical efficacy.