We have studied the skin irritation produced by the prolonged application of transdermal therapeutic systems. The systems were applied to the skin of the back of male volunteers for 120 hours, and sweat accumulation and bacterial growth were studied. In some cases hydrogel discs were attached to the systems. The results showed that sweat accumulation contributed more to the skin irritation than the bacterial overgrowth. The incorporation of hydrogels in the transdermal delivery system may help to reduce skin irritation by absorbing water.