There are very few reports on hypersensitivity reactions in association with titanium-based materials so that the existence of allergy to titanium is still put in question. We report on a patient in whom impaired fracture healing and eczema localized to the perioperative area developed upon titaniumbased osteosynthesis. Patch testing gave no reactions to titanium nor to nickel, chromium, or cobalt. However, in the lymphocyte transformation test, the patient's lymphocytes showed markedly enhanced proliferation in vitro to titanium. After removal of the titanium material, fracture healing was achieved and the eczema cleared. Parallel to this, in vitro hyperreactivity to titanium disappeared. Although contact allergic reactions to titanium have been very rarely reported, these findings support a diagnosis of titanium allergy in our patient. Metallic alloys are used in large number for osteosynthesis and long-term implants. In association with stainless-steel-based and cobalt-based materials, contact hypersensitivity reactions have been described and were mostly attributed to chromium, cobalt, nickel, and occasionally to molybdenum. In contrast, due to its excellent biocompatibility (1), titanium is not considered to provoke allergic reactions. However, in view of the few reports on contact dermatitis or granulomatous reactions to titanium upon its use in pacemakers or implants (2-4), the discussion about 'titanium allergy' is still ongoing. Patients and MethodsA 35-year-old male was referred for evaluation of suspected hypersensitivity to implant materials. He presented with a several months history of hand eczema and failure of healing of a hand fracture. Eczema had started within few weeks after an osteosynthesis of right metacarpal fracture by use of a pure titanium miniplate and screws. The patient had gradually developed itching, erythema, and scaling of the right hand together with a vesiculopapular eruption on several fingers, mainly on their ventral parts. Over the next weeks, lesions extended also to the left hand ( Fig. 1) and proximal part of the forearms. There was a history of seasonal rhinoconjunctivitis and asthma but not of previous contact or atopic eczema or hypersensitivity reactions to metals. The patient was otherwise healthy. Under the diagnosis of contact dermatitis, a corticosteroid-containing cream was prescribed and patch testing was planned. Patch testing was performed according to the guidelines of the German Contact Dermatitis Research Group on the patient's upper back with the following series: standard, vehicles, disinfectants, and preservatives. In addition, TiO 2 was tested. Evaluation of the reactions was done after 2, 3, and 7 days. Removed implant materials were not available for subsequent, additional testing.For the lymphocyte transformation test, peripheral blood mononuclear cells (PBMC) were isolated from heparinized blood samples of the patient and a healthy control, as well as of 49 additional controls over the next months. Within