BACKGROUND Natural rubber latex (NRL) allergy remains an important allergic disease triggering urticaria, asthma, angioedema and anaphylaxis. Specific immunotherapy can help to solve problems related to NRL allergy. So far, no controlled clinical trials have been performed in children suffering from NRL allergy. OBJECTIVE To evaluate the safety and efficacy of sublingual immunotherapy (SLIT) with a commercial NRL extract in children with NRL allergy. METHODS Randomized, double-blind, placebo-controlled, 12-month trial. METHODS Twenty-six children (aged 4-15 years) with NRL allergy, who had cutaneous and/or respiratory symptoms, including oral allergy syndrome to fruits containing cross-reactive allergens, were recruited. Twelve children were randomized to SLIT with a commercial NRL extract and eight to placebo (3:2). An additional six children with NRL allergy served as untreated controls. METHODS A glove use test was utilized to monitor skin and systemic symptoms triggered by NRL exposure at baseline and 3, 6, 9 and 12 months later. Oral allergy symptoms were also monitored. RESULTS No side effects related to treatments were observed in any patient. A significant improvement of symptom score in treated patients in comparison with baseline values was observed at 3 months (p = 0.01) and consolidated after 1 year of treatment (p = 0.0005). In comparison with placebo, significant improvements were observed starting at 9 months from study start (p = 0.015) and at 12 months (p = 0.005). The number of foods triggering oral allergy symptoms increased in placebo and control subjects, but not in active treated patients (p = 0.05). CONCLUSIONS Latex SLIT was safe and efficacious in paediatric patients with NRL allergy.