The rationale for using essential oils to alleviate headache is based on several assumptions. Especially for peppermint oil certain analgesic mechanisms were recently described. Local application of peppermint oil generates a long-lasting cooling effect on the skin, caused by a steric alteration of the calcium channels of the cold-receptors. Further it was shown that peppermint oil inhibits non-competively 5-hydroxytryptamin (Serotonine) and substance P induced smooth muscle contraction in animal-models. It is also known that peppermint oil induces a significant increase of the skin blood flow of the forehead after local application, measured by laser doppler. Assuming that a clinical relevant analgesic action exists, this ought to be observable in experimental algesimetric human tests. Therefore the effects of peppermint oil and eucalyptus oil preparations on neurophysiological, psychological and experimental algesimetric parameters were investigated in 32 healthy subjects in a double-blind, placebo-controlled, randomized cross-over design. Four different test preparations were used: preparation 1 (LI1701) consisted of 10 g peppermint oil and 5 g eucalyptus oil plus ethanol 90% to 100 g; preparation 2 (LI1702) of 10 g peppermint oil and traces of eucalyptus oil plus ethanol 90% to 100g; preparation 3 (LI1703) of traces of peppermint oil and 5 g eucalyptus oil plus ethanol 90% to 100 g; and preparation 4 (placebo) of traces of peppermint oil and traces of eucalyptus oil plus ethanol 90% to 100 g. The test preparations were applied to large areas of the forehead and temples using a small sponge. The treatment effect of the preparations was evaluated by comparing baseline and treatment measurements. The combination of peppermint oil, eucalyptus oil and ethanol can increase cognitive performance while having a muscle-relaxing and mentally relaxing effect, but has little influence on pain sensitivity. A significant analgesic effect with a reduction in sensitivity to headache is however produced by the combination of peppermint oil and ethanol. The essential plant oil preparations can thus be shown by laboratory tests to exert significant effects on mechanisms associated with the pathophysiology of clinical headache syndromes. Further, to investigate the efficacy of essential oil preparations compared to usual analgesics (paracetamol or acetylsalicylicacid) a double blind, placebo controlled, randomized study should be performed.