Background. Nickel contact allergy remains common in Western countries, and the dermatitis may require prolonged treatment. The development of new strategies aimed at improving the quality of life of affected individuals is needed. Objectives. To investigate the efficacy of oral hyposensitization in nickel-allergic individuals and how this affects in vitro T cell responsiveness to the metal. Methods. Twenty-eight nickel-allergic patients received a daily dose of 50 μg of elemental nickel (given as NiSO 4·6H 2O) in cellulose capsules for 3 months. Severity of clinical manifestations, in vivo nickel responsiveness and in vitro T cell responses to the metal were assessed after 1 and 3 months. Results. Twenty-six patients finished the study. In these patients, oral hyposensitization ameliorated clinical manifestations despite continued nickel exposures, and increased the threshold of skin responsiveness to nickel. The 12 enrolled patients in the immunological study showed decreased in vitro T lymphocyte responsiveness to the metal, in terms of both cell proliferation and cytokine release. In the 1-year follow-up, 50% of the patients experienced relapses of the clinical manifestations at sites of topical exposure to nickel. Conclusions. Our study suggested therapeutic efficacy of oral hyposensitization in allergic individuals. Placebo-controlled studies are required to confirm the results and determine the optimal therapeutic regimen for prolonged beneficial effects.