BACKGROUND Sodium cromoglicate (SCG) has long been used in the management of allergic diseases, including as an ointment for atopic dermatitis. Although mast cell stabilization was initially considered as its mechanism of action, anti-inflammatory actions and modulation of sensory nerve function have also been suggested. OBJECTIVE To investigate the mechanism(s) by which SCG relieves allergen- and histamine-induced dermal inflammation by assessing its effects on pruritus, flare, skin temperature and weal volume. METHODS Aqueous cream containing 0.2%, 1% or 4% SCG or no SCG (placebo) was applied in a randomized single-blind manner to four areas on each forearm (two sites per arm) and covered with an occlusive dressing. One hour later, skin-prick tests were performed in 20 allergic subjects with allergens to which they had previously shown sensitization, and in 40 nonallergic subjects with codeine (9 mg mL(-1), 20 subjects) and histamine (10 mg mL(-1), 20 subjects). Weal volume, skin temperature increase, erythema area and pruritus intensity were assessed at 0, 5, 10 and 15 min. RESULTS SCG significantly (P < 0.05 to P < 0.001) reduced pruritus induced by all stimuli, with 4% SCG being most effective. Significant (P < 0.05 to P < 0.01) reductions of erythema area were also seen but there was no inhibition of weal volume or temperature increase. CONCLUSIONS SCG is effective in reducing pruritus but has no effect on weals, supporting the proposition that, in the skin, SCG inhibits sensory C-fibre nerve activation rather than preventing mast cell degranulation. We suggest that topical SCG treatment, delivered in an appropriate vehicle, may be beneficial for symptomatic relief of pruritus in patients with cutaneous mastocytosis and other pruritic dermatoses.