The skin on the lower legs of 25 female subjects was evaluated first in the winter, and then again in the summer of the same subjects. Barrier function was determined by measuring transepidermal water loss (TEWL), and skin hydration and dryness were evaluated by electrical measurements (Corneometer ® CM825) and visual grading. Stratum corneum (SC) was sampled using 10 sequential D-Squame sampling discs and analyzed for 2-pyrrolidone-5-carboxylic acid (PCA), keratin-1,10,11, interleukin 1α (IL-1α), interleukin 1 receptor antagonist (IL-1ra), selected ceramides, cholesterol, cholesterol sulfate, and selected free fatty acids. TEWL as well as the visual dryness grades were significantly lower in the summer while hydration was higher. PCA was significantly higher in the summer as were the keratins. The ratio IL-1ra:IL-1α, an indicator of skin inflammation, was significantly lower in the summer. The amount of protein removed by the tape strips was also significantly lower in summer indicating better SC cohesion. Among the SC lipids measured, total ceramides, individual ceramides, total fatty acids, and cholesterol were higher in summer compared to winter. Stearic acid and cholesterol sulfate were not significantly different between winter and summer.