Amphiphilogels, gels that consist solely of non-ionic surfactants, are being developed as dermal/transdermal drug delivery vehicles in our laboratories. The irritation potential of two amphiphilogels was investigated on shaved mouse skin, in vivo, and compared to those of Aqueous Cream BP (a moisturiser) and 5% sodium lauryl sulphate (SLS) solution (a known irritant). The skin irritation potential of one of these gels was then investigated in human, using Aqueous Cream BP as a negative control. Skin irritation (following daily application of gels and of controls for 5 days) was assessed by laser Doppler velocimetry, a visual erythema scoring method, and histological evaluations of excised mice skin. We found that the amphiphilogels caused no significant increase in blood flow and in epidermal irritation. In contrast, the SLS solution caused significant perturbation to mouse skin. From this study we conclude that these amphiphilogels may be used as dermal/transdermal drug delivery vehicles.