An open-label, randomised, parallel-group efficacy study was designed to compare Betadine cold sore paint and Stoxil topical ointment for the prevention of shedding of herpes simplex virus (HSV) from cold sores. Seventy-two patients aged 18-61 years (mean 32.2 years), with symptoms indicating recent onset of herpes labialis, were entered into the study. Patients were randomised to receive Betadine cold sore paint, Stoxil topical ointment or no treatment. To detect infectious virus, swabs were taken for virus culture before and 2 h after treatment. The no-treatment control group was included to monitor the efficiency of the swabbing technique. The primary measure of efficacy was the proportion of patients in each group returning a swab positive for HSV prior to treatment application and negative for HSV 2 h after treatment application. All 72 patients completed the study. HSV clearance rates were 0.636 for the Betadine treatment group and 0.092 for the Stoxil treatment group (p = 0.00056). It was concluded that recovery of infectious HSV from the lips of patients who applied Betadine cold sore paint to their lesions was significantly lower than from patients who applied Stoxil topical ointment.