Cytokines have been proposed as histamine-independent itch mediators. To investigate this hypothesis, single doses of interleukin-2 (IL-2, 10MU/mL) and tumour necrosis factor α (TNF-α, 10 μg/mL) were delivered to the epidermis of 10 healthy volunteers with a controlled skin-prick model; 1% histamine and solvent controls were included in a double-blind, randomized crossover design. Itch ratings (computerized visual analogue scale) were obtained every 20s for 15 min and cutaneous reactions (weal, flare and temperature) were measured. Reactions were also recorded after 2, 24 and 48 h. The mean itch ratings were: histamine 35·5, IL-2 3·3 (both P<0·01 compared with control), TNF-α 1.6 and solvent control 1.75 (not significant). Weal and flare occurred only with histamine. In two volunteers, an inflammatory papule with transient pruritus developed 12–18 h after applying IL-2. In conclusion, IL-2 showed a rapid, low pruritogenic effect, which may be followed by an inflammatory response. TNF-α induced no itching in this setting. Skin-prick testing with appropriate doses of potential pruritogens provides a safe and sensitive model for further chemoreceptor studies.