The effect of topical applications of pyrrolidone carboxylic acid (PCA), sodium lactate (NaL) and urea on in vivo transepidermal water loss (TEWL) in healthy volunteers was studied. The moisturizing compounds were applied both singly and as mixtures using a 2(2) factorial design. It is shown that all three compounds increased TEWL and that moreover, urea and PCA exerted synergism. No such interaction was observed between urea and sodium lactate. The study provides a rational basis for the co-formulation of urea and PCA in moisturising products for topical use.