Several studies have shown that oral nickel exposure can elicit systemic contact dermatitis (SCD) in nickel-sensitive individuals. The current study describes some of the immunological mechanisms underlying such nickel-allergic reactions elicited by oral exposure to nickel. Following oral exposure to graded concentrations of nickel or placebo, blood samples were taken from nickel-sensitive individuals and from non-nickel-sensitive controls. T-cell subtypes (CD3+, CD4+, CD8+ and CD45RO+), expression of skin-homing receptor, cutaneous lymphocyte-associated antigen (CLA) and cytokine profiles [interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, interferon-gamma and tumour necrosis factor-alpha] were investigated. A definite dose-response reaction pattern to oral nickel exposure was observed among nickel-sensitive individuals. Nickel-sensitive individuals whose dermatitis flared after oral challenge with nickel showed significant decreases in fractions of CD3+ CD45RO+ CLA+ and CD8+ CD45RO+ CLA+ blood lymphocytes, suggesting migration of CD8+ 'memory' CLA+ T lymphocytes from the blood to peripheral tissues. Only those nickel-sensitive individuals who clinically reacted to oral challenge with nickel (4 mg) had elevated levels of IL-5 in the serum, indicating an activation of type 2 T lymphocytes in the peripheral blood. In conclusion, the study indicates that CD8+ CD45RO+ CLA+ T lymphocytes and T lymphocytes with a type 2 cytokine profile are involved in SCD elicited by nickel.