Ultrastructural and volume variations in intact human epidermis due to differences in composition of the fixative have been investigated by electron microscopy and stereology. It was found that with glutaraldehyde as fixative variations in buffer osmolality in the range of 120-390 mosmol caused readily detectable changes in volume of the intercellular space and keratinocyte morphology. Also the epidermal Langerhans' cell was effected by variations in buffer osmolality. Three commonly used fixatives (glutaraldehyde, glutaraldehyde + paraformaldehyde, and osmium tetroxide) were found to result in different morphological and volume relations.