Skin penetration by Necator americanus larvae has been investigated in vitro. Larvae were able to penetrate completely human skin from both the epidermal and dermal directions; their passage through the epidermis was marked by cellular destruction. Removal of chloroform soluble skin lipids affected both the percentage of larvae invading and the percentage exsheathing. The larvae released an enzyme at about 37 degrees C, which showed peak activity against azocoll at 37 degrees C and pH 8. It is suggested that initial invasion is a mechanical process and that the enzyme is functional in passage through the germinal layers of the epidermis.