Early treatment of recrudescent herpes labialis over the symptomatic area has been claimed to inhibit the clinical signs of recrudescent herpes labialis. Electronic infrared thermography can both recognise the prodromal phase and identify the area requiring drug therapy. Our objective was to use infrared thermography to identify prodromal herpes and follow the response to topical acyclovir cream therapy over the thermographically active area. Seventy instances of prodromal cold sores were confirmed thermographically. Zovirax cold sore cream (acyclovir) was applied 5 times per day for 5 days to the thermographically positive area. All returned after 72 h for a further thermographic and clinical examination of the initially active area. All 70 patients illustrated a localised increase in temperature over the symptomatic area during the prodromal stage. The development of a clinical herpes lesion was prevented in 46% of the patients. In the lesions that did develop, an 80% reduction in clinical lesion size was observed in 82% of the subjects. The remaining 18% showed a reduction in healing time.