Very few double-blind trials of oral immunotherapy have been reported. The majority of these have been performed with pollen extracts and the results have often been equivocal. The major weaknesses of these studies have been the short periods of the trials, the low doses of allergen employed and inadequate evaluation of efficacy. The present study has involved a placebo-controlled double-blind trial of oral immunotherapy for three years with Dermatophagoides pteronyssinus at relatively high doses in 18 paediatric patients. Throughout the trial clinical parameters (symptom and medication scores) and immunological parameters (specific IgE, IgG1 and IgG4 levels) were monitored in order to assess the safety and efficacy of the treatment. The treatment was well tolerated by all patients and no side-effects were experienced. Clinical improvement was evident after the second year of therapy and this was confirmed by a significant reduction in conjunctival reactivity assessed by a specific conjunctival provocation test. In addition, there were significant changes in the immunological parameters with a reduction in specific IgE and increased levels of IgG4 and IgG1, results in keeping with previous studies of oral and subcutaneous immunotherapy. Although the results do not provide an explanation of the basis of successful oral immunotherapy, they clearly demonstrate the efficacy and safety of the treatment and suggest that it may be a useful and more acceptable alternative for patients than the traditional subcutaneous immunotherapy.