Transmission electron microscopy (TEM) was used to clarify the effect of topically applied 20% azelaic acid (AA) on acne vulgaris lesions. Twenty male acne patients were included in this study. A punch biopsy was taken from each patient before treatment and from five of the treated patients. After 2 months of treatment with 20% AA, the pattern of follicular keratinization was markedly altered. In particular, there was a reduced thickness of the horny layer, a mild decrease in tononlaments and a marked reduction in the number and size of keratohyaline granules. Enlargement of perinuclear rough endoplasmic reticulum (RER) and swollen nitochondria were frequently observed. A reduction in the dermal inflammatory infiltrates was frequently identified. Very few bacteria were detected in the lumen. These findings confirm the antikeratinizing effects of 20% AA on acne vulgaris lesions.