This study investigates lymphocyte subsets in both the gastrointestinal mucosa and blood, in patients with nickel allergic contact dermatitis, after 10 mg oral nickel challenge (double-blind, placebo-controlled). 6 such patients with cutaneous symptoms induced only by skin contact with nickel (group A), 6 with a flare-up of cutaneous symptoms after food nickel ingestion (group B) and 6 healthy controls (group C) were enrolled. Blood lymphocyte subsets (CD4, CD45RO, CD8) were analyzed before and after 4 and 24 h from the challenge (test 1, 2, and 3), and intestinal biopsies were performed 2 days later. Challenges were positive in group B and negative in group A and controls. Serum and urine nickel levels significantly increased after nickel ingestion, with no differences between the 3 groups. At test 3, a significant decrease of the all CDs studied was found in group B. Biopsies of this group showed higher levels of CD45RO+ cells in the lamina propria and in the epithelium and lower levels of epithelial CD8+ lymphocytes. This study confirms that ingested nickel may induce flare-up of cutaneous reactions in some nickel-allergic patients, independently of the degree of sensitization and the intake of metal. In these patients, oral nickel stimulates the immune system, inducing maturation of T lymphocytes from virgin into memory cells; these latter cells seem to accumulate in the intestinal mucosa. The immunoreaction also involves CD8+ cells, whose role is not yet clear.