Background: Although pruritus is common in scalp skin, the forearm has been the main site for investigation in previous experimental studies. Objective: Our purpose was to compare the sensitivity to pruritic stimuli in human scalp and forearm skin. Methods: Four microdialysis fibers were inserted intradermally into scalp (n = 10) or forearm skin (n = 10) of healthy male subjects and were perfused with histamine (0.01%) or compound 48/80 (C48/80; 0.05%) for 20 minutes. Total protein content in the dialysate was assessed at 10-minute intervals. Intensity of itching and pain sensation were measured psychophysically. Results: Histamine- and C48/80-induced protein extravasation was significantly lower in scalp skin. Histamine and C48/80 invariably provoked an itching sensation in the forearm but only in 4 of 10 applications in the scalp. Conclusion: Despite the high prevalence of pruritus, scalp skin is less sensitive to histamine-induced experimental itching. A lower innervation density of pruritic nociceptors and/or different central processing of itching might account for this difference. (J Am Acad Dermatol 2002;47:245-50.)