At some vaccination centres, it seems to be a clinical observation, that there is a reduction in the number of attacks of herpes labialis following yellow fever vaccination. We therefore conducted a double blind, prospective, randomized study to evaluate the efficacy of yellow fever vaccination against recurrent herpes labialis. Twenty-four patients with culture proven herpes labialis were allocated to either yellow fever vaccination or placebo (saline), with 12 persons in each group. After vaccination/ placebo the patients were followed for one year. The patients returned a letter every other month with information concerning the number of attacks during the period. Comparison of the data from the two groups after one year revealed no significant difference in the number of attacks between the two groups. In conclusion evaluation of the data from this study does not confirm the clinical observation that yellow fever vaccination may act as prophylaxis against herpes labialis.