Little is known about the clinical and immunological changes in the nickel allergic patients with systemic symptoms. We aimed to evaluate T helper cell responses of patients with different clinical presentations due to nickel. Patients having various allergic symptoms and positive patch test results to nickel and 20 controls underwent skin prick tests with nickel. IL-10, IL-4, IL-5 and IFN-gamma were measured in the culture supernatants of PBMC stimulated by nickel during lymphocyte proliferation test (LTT). 69 patients (56 female, mean age: 49.2 ± 13.1), 97% having nickel containing dental devices and 20 controls (8 female, mean age 34.9 ± 12.06) were evaluated. Skin prick tests with nickel were positive in 70% of the patients (p<0.001), being significantly higher in the patients with urticaria/angioedema (p=0.02). The LTT stimulation index (p<0.0001), IL-4 (p=0.002), IFN-gamma (p=0.01), IL-5 (p=0.04) and IL-10 (p=0.003) were higher in the patient group. LTT stimulation index, IL-4 and IL-10 were significantly elevated in patients having urticaria, angioedema and respiratory symptoms when compared to those who had only oral symptoms or systemic dermatitis (p=0.004, p=0.002 and p=0.01, respectively). This study suggests the presence of Type I hypersensitivity in addition to a Type IV immune reaction in patients with chronic systemic symptoms related to nickel. Nickel containing dental alloys and oral nickel intake seem to trigger systemic symptoms in previously nickel sensitized patients.