Use of alpha hydroxy acids (AHA) to ameliorate specific dermatological, problems with keratinization has become fairly widespread. The aim of this study was to evaluate the effects of the AHA derivative of glycolic acid, applied in different dosages, on rat skin using tight and electron microscopy. Skin biopsies were taken from the dorsal side of rats (n = 16) and at the end of each week after applying solutions containing AHA: week 1, 8% (n = 5); week 2, 50% (n = 5); week 3, 70% (n = 6). The skin samples were fixed in 10% formalin for histology and 2.5% glutaraldehyde solution for electron microscopy and processed using routine protocols. Histological sections were stained with hematoxylin and eosin (H-E), Masson's trichrome and were also Labelled for binding of a primary antibody against collagen I using the avidin-biotin-peroxidase method. The epidermal thicknesses were measured and the fibroblast count of the dermis was taken and the results compared using the statistical ANOVA test. Semi-thin sections were stained with toluidine blue-azure II solution and ultrathin sections were contrasted with uranyl acetate and lead citrate. Histochemical and immunohistochemical observations demonstrated that AHA treatment resulted in statistically significant increased thickness of the epidermis and an increase in numbers of active fibroblasts and in the amount of dense collagen, especially at higher dosages of AHA. Ultrastructural examination of rat skin from AHA-treated groups showed cytoplasmic vacuolization in epidermal keratinocytes, intercellular dysjunctions, and increased quantities of organized bundles of collagen fibers in the dermis. The use of AHA in appropriate dosages has been found to play an important role in the treatment of specific skin disorders, however, the harmful effects of use of AHAs at higher concentrations should not be ignored. We conclude that alpha hydroxyl acids have a wide spectrum of use in the field of dermatology but, due to side-effects, their use, dosage, and time frame should be restricted to the advice of dermatologists. (C) 2006 Elsevier GmbH. All rights reserved.