The primary function of surfactants is to remove dirt, exfoliated corneum cells, and microorganisms from the skin. However, the use of toiletries such as soaps and shampoos containing surfactants may cause adverse effects such as cutaneous irritation, dryness, and itching. Recently, skin pathologies, including dry skin, rough skin, and sensitive skin, have increased because of changes in living conditions and lifestyle. Although many people with skin pathologies complain of itching during and/or after skin washing using detergents, the mechanisms of detergent-induced itch are yet to be elucidated. Therefore, in this study, we investigated the mechanisms underlying surfactant-induced itching. We found that topical application of an anionic surfactant sodium laurate at an alkaline pH, but not N-lauroylsarcosine sodium salt at neutral pH, to mouse skin induced scratching, an itch-related response. Additionally, we found that the sodium laurate-induced scratching was inhibited by H(1) histamine receptor antagonist, but not mast cell deficiency. Sodium laurate application increased histamine content and the level of the active form (53 kDa) of L-histidine decarboxylase (HDC) in the mouse epidermis, but not the dermis. Furthermore, addition of sodium laurate to a human epidermal cell culture increased histamine release and HDC levels, without affecting cell viability. These results suggest that surfactants with alkaline properties are pruritogenic and that the pruritus is induced by the histamine released from epidermal keratinocytes. The increase in histamine release may be attributable to the activation of HDC in epidermal keratinocytes.