An in vivo method was developed to measure the effectiveness of skin protective creams against 2 dye indicator solutions: methylene blue in water and oil red O in ethanol, representative of model hydrophilic and lipophilic compounds. 3 representative barrier creams commercialized as effective against lipophilic, hydrophilic, or lipophilic and hydrophilic substances were assayed by measurements of the dye in cyanoacrylate strips of protected skin samples after various application times. The flexural surfaces of the forearms of 6 normal volunteers (3 female and 3 male, mean age 26.8 +/- 4.1 years) were treated. The method was as follows: solutions of 5% methylene blue in water and 5% oil red O in ethanol were prepared, and applied to untreated skin and protective-cream-pretreated skin with the aid of aluminum occlusive chambers, for 0 h and 4 h, respectively. At the end of the application time, the creams were removed. Consecutive skin surface biopsies (SSB) from 1 to 4 strips were taken. The amount of stain in each strip was determined by colorimetry, and the cumulative amount of stain from 1 to 4 strips in each measurement was calculated. The cumulative amount represents the amount of permeation of each solution at each time point, and the efficacy of skin barrier cream. The results showed one formulation at both 0 h and 4 h reduced the amount of permeation of methylene blue (p < 0.01) and oil red O (p < 0.01) compared with the control group. Another formulation was protective against the permeation of oil red O (p < 0.01), but not against methylene blue at 0 h and 4 h; it was not significantly different at 0 h versus 4 h. The 3rd formulation produced increased cumulative amounts to oil red O at both 0 h and 4 h (p < 0.05); it also increased permeation amounts to methylene blue (p < 0.05) after 4 h. This model appears a facile, rapid and objective early screen to evaluate the efficacy of skin barrier creams in vivo, as well as their individual ingredients.