Background: In this study we have taken an interest in systemic exposure to nickel in patients with delayed hypersensitivity to nickel. Objective: The aim of the study was to more closely investigate the importance of factors such as ingested nickel dose, time interval between nickel patch testing and oral nickel challenge as well as degree of nickel hypersensitivity in relation to flare-up reactions. Methods: Thirty nickel-sensitive female subjects were patch tested with a serial dilution of nickel sulfate in water on 4 different test occasions during a period of 7 months. One month after the last patch test the patients were randomly divided into 3 different groups. The patients in the groups were challenged orally with a placebo capsule, 1.0 mg nickel, or 3.0 mg nickel. Results: None of the patients challenged with placebo had flare-up reactions of earlier patch test sites, but 2 of the patients challenged with 1.0 mg nickel and all of the patients challenged with 3.0 mg nickel had flare-up reactions. There were significantly more flare-up reactions of the most recent patch test sites (1 month) compared with the most distant (8 months) test sites. There was also a statistically significant positive correlation between the intensity of previous positive patch tests and the flare-up reactions. Conclusion: In the assessment of the possibility of systemic allergic contact dermatitis from nickel, the dose as well as the intensity and time since previous nickel eczema have to be considered. (J Am Acad Dermatol 2001;44:616-23.)