The aim of this study was to investigate the relationship between psychological stress and negative mood and the recurrence of herpes simplex (HSV1). A range of standard, baseline measures of health and psychological well-being were collected from 20 participants who suffered from HSV1 recurrences (with a history of recent recurrence) and 18 matched controls. Longitudinal data was collected over a 16-week period using weekly diaries. Participants recorded weekly levels of psychological stress, negative mood, negative events and hassles and kept a weekly health record documenting the recurrence of HSV1 and the incidence of other infectious illness. The longitudinal relationship between stress, negative mood and recurrence of HSV was assessed. Participants who suffered from frequent HSV1 recurrences were significantly higher on standard measures of stress and negative mood than those who only suffered occasional or no recurrences. Furthermore, there was a longitudinal relationship between high levels of perceived stress and the recurrence of HSV1.