H(1)-receptor antagonists are known to suppress reactions in skin-prick tests (SPTs); however, the effect of H(2)-receptor antagonists, which are widely used in our everyday practice, remains unclear. The aim of this study was to determine the influence of ranitidine on wheal, flare, and itching sensation in SPTs. Twenty-one atopic patients (5 women and 16 men) with an average age of 28.04 years (SD, +/-8.24) were tested with histamine, codeine, negative control solution, and standard allergen extracts. Ranitidine (150 mg daily), loratadine (10 mg daily), or placebo were given to the volunteers for 5 days in a double-blind manner with 14 days of washout period. SPTs were applied to the volar surface of a forearm. There was no difference in wheal, flare, and itching between SPTs performed after placebo and washout period. The analysis revealed a statistically significant suppression of wheal and flare by ranitidine and loratadine (p = 0.013 and <0.00001, respectively, for wheals after allergens solutions tests, Wilcoxon rank-sum test). We found a significant suppression of itching induced by ranitidine (reduction of 26.85%; p = 0.005) and loratadine (29.6%; p = 0.005) as compared with placebo (p = 0.068 versus washout). Our data show a suppressive effect of ranitidine on the wheal, flare, and itching sensation in SPT. Because the sensitivity and specificity of skin testing requires withholding medication that could change the skin reactivity, it seems important to take into account the possible influence of H(2)-receptor antagonists on allergy diagnosis and therapy.