This preliminary study demonstrated the applicability of fluorescence CLSM for a detailed study of experimental skin irritants in vivo. Essential findings were disturbed and widened cell borders, swelling of keratinocytes by PA and induction of a parakeratotic shift by SLS with clusters of keratinocytes holding nuclei in the epidermis. Fluorescence CLSM offers a unique opportunity to study the inter- and intracellular water compartments directly in the epidermis in situ and an opportunity to visualize cell proliferation manifested as parakeratosis. Fibre-optic fluorescence CLSM of irritant reactions is, however, technically more complicated than reflectance CLSM and may not be applicable to any irritant. SLS applied epicutaneously interacted with the skin surface and coupling to the microscope and was thus found to be more difficult to study technically than PA. PA dissolved in isopropanol is for technical reasons, and with SLS as alternative, considered the preferred model irritant.