Mechanical wounding was shown to activate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in the skin of transgenic mice. Both noninvasive rubbing and scratching of the skin resulted in a range of 4- to 44-fold increased levels of luciferase reporter gene activities when assayed 24-48 h after wounding. Moreover, long-term noninvasive rubbing each day for 17 days resulted in similar increased levels of luciferase activity. Experiments were done to determine whether the HIV-1 LTR-luciferase transgene might be activated when pups were nursed on the mammary tissues of transgenic mice. Luciferase reporter gene activity in mammary glands skin following nursing was significantly higher than in skin from non-pregnant transgenic mice or transgenic mice 20 days post-conception, which suggests that the natural abrasive action of nursing resulted in activation of the LTR. These results may have implications for sexual transmission and maternal-to-infant transmission of HIV-1.