Patients with eczema and other dry skin conditions use moisturizers also when the skin appears healthy. However, moisturizers have been found to change skin barrier function, and it appears that certain combinations of ingredients increase the skin susceptibility to external agents. In the present randomized and single-blind study, the influence of a urea-containing cream on nickel susceptibility in 35 patients with known allergy to nickel was evaluated. Treatment of the volar forearm twice daily for 20 days with the urea cream reduced transepidermal water loss (TEWL). However, the susceptibility to nickel sulfate was not changed by the cream treatment. Clinical scoring of the skin reaction did not show any difference between the untreated and the cream-treated area. Furthermore, the increase in TEWL did not differ between the areas. The absence in correlation between TEWL and skin susceptibility to nickel suggests different penetration pathways through the skin of water and nickel. Measurement of the skin permeability to other substances than water is pertinent to the understanding of the influence of moisturizers on the skin permeability and, ultimately, to their therapeutic efficacy in the prevention of contact eczema due to exposure to harmful exogenous substances.