Xerotic skin is a pattern of reaction to a variety of disorders (eg, winter xerosis, hereditary ichthyosis) with abnormalities of desquamation in common. The trial described in this article was a double-blind randomized-comparison clinical trial investigating the effect of pure lanolin versus ammonium lactate 12% cream in treating moderate to severe foot xerosis. Xerosis was clinically assessed at baseline visit, and designated sites were reevaluated after 1, 2, and 4 weeks of therapy. Ninety-two patients were enrolled; 41 of these were excluded from analysis (25 were lost to follow-up, 8 were noncompliant, 1 was discharged from study because of an adverse event after visit 1, and 7 were noncompliant after visit 2). Although there was significant improvement in xerosis scores for both treatment groups after 2 and 4 weeks of treatment, no differences were statistically significant. Used twice daily for 4 weeks, pure lanolin and ammonium lactate cream were both effective in treating moderate to severe xerosis.