BACKGROUND Although healthy persons often report on reactions to homeopathically diluted substances, the mechanism behind such reactions remains unclear. This study examines whether a distinction can be made between the short-term reactions of healthy volunteers to a homeopathically diluted substance - Aconitum napellus C30 - and to a placebo. METHODS From the 33 subjects randomized for this double-blind, placebo-controlled crossover study, 27 could be included in the analysis. The study comprised two 7-day-long treatment periods, each including the intake of a study preparation for 3 days and a wash-out period of 4 days. One group was first treated with Aconitum napellus C30 and then with placebo; the other group received the two study preparations in the reverse order. The signs and symptoms before the first treatment and after each treatment were collected, evaluated, weighted and repertorized. Based on this classification the blinded physician assessed these signs and symptoms as study outcome parameter to represent the responses to each of the study preparations. Statistical analysis of the data was performed using the Wilcoxon-Mann-Whitney rank test. RESULTS Crossover differences yielded statistical significance between the classified reactions towards Aconitum napellus C30 and to placebo (p = 0.004). CONCLUSIONS A clear difference between the reported short-term reactions of healthy subjects towards Aconitum napellus C30 and towards placebo was shown. The crossover design with intra-individual comparisons proved to be adequate to recognize the study preparations and for the statistical analysis of a small population sample.