Background: After primary orofacial infection with the herpes simplex virus (type 1, HSV-1), up to 40% of HSV seropositive subjects suffer recurrent herpes infections which are characterized by painful erosions of the involved skin mainly around the lips (herpes labialis). Besides various other factors, there is growing evidence suggesting that psychosocial factors might trigger HSV. The present study was designed to investigate modulation of recurrent HSV infection by experimentally induced emotional distress. Methods: Among patients with herpes labialis (n = 91), subjects who showed recurrent HSV infection (>5 acute infections/year) and who reported to suffer from HSV symptoms exclusively after confrontation with dirty dishes, i.e. dirty plates or dirty glasses were selected by standardized interview. Subjects (n = 20) were randomly assigned to two treatment groups. The experimental group (n = 10) was first exposed to 5 slides showing dirty glasses and subsequently to the glasses previously presented on the slides in vivo. The control group (n = 10) was exposed to neutral slides and neutral objects. In order to determine the proportion of leukocyte subpopulations and concentrations of tumor necrosis factor α (TNF-α), blood samples were collected 15 min before as well as 40 min and 48 h after stimulus presentation. Saliva cortisol was obtained 45, 20, 15 and 1 min before and 1, 10, 20 and 30 min after stimulus confrontation. Results: Medical examination of the volunteers 48 h after the experiment indicated that four experimental subjects showed HSV-1 symptoms while not a single herpetic infection could be determined in the control subjects (p = 0.033). Moreover, significantly elevated concentrations of TNF-α were observed in the experimental, but not in the control group. No significant alterations of the number of leukocyte subpopulations were found 30 min or 48 h after stimulus presentation. Further, cortisol concentrations were found to be unchanged after the treatment. Conclusions: The present findings suggest that experimentally induced emotional stress such as disgust may be associated with reactivation of HSV.