BACKGROUND The benefit of alcohol-based disinfectant used on normal skin has been debated. OBJECTIVE The objective of the present study was to compare the effects of repeated exposure to an alcohol-based disinfectant, a detergent and an alcohol-based disinfectant/detergent alternately for 10 days, including noninvasive measurements in the evaluation. Skin reactivity in irritated skin after a 4-week interval was also evaluated. METHODS Detergent, disinfectant and alternate disinfectant and detergent were applied twice daily every 10 min for 1 h to the ventral upper arms and forearms of 17 healthy volunteers. A control area was included. After 4 weeks an SLS patch was applied to each area. Irritant reactions were quantified with a visual score recording and measurements of transepidermal water loss (TEWL) and skin colour were performed on days 1, 5, 11, 38 and 40. RESULTS On day 5 the detergent caused a higher visual score than either disinfectant applied alone or alternate disinfectant and detergent, P < 0.05. On day 11 detergent and alternate disinfectant and detergent caused a higher score than disinfectant, P < 0.05. An increased irritant response for detergent compared with disinfectant alone and alternate disinfectant and detergent was confirmed by TEWL evaluations on days 5 and 11, P < 0.001, while no significant difference was found by colour measurement. After 4 weeks, when evaluated by colour measurement, significantly less response to the SLS patch was found on the disinfectant-treated area compared with the control area and detergent area, and a similar trend was found for TEWL, although it was not statistically significant. CONCLUSIONS Alcohol-based disinfectant caused less visible skin irritation and less skin barrier disruption than the use of detergent. The alternate use of detergent and disinfectant caused less irritation than the use of detergent, and a possible interaction between the two irritants was not indicated. After 4 weeks there was a tendency for decreased skin reactivity in the skin areas which had 4 weeks previously been exposed to disinfectant.