Recently we have shown that T-cell-mediated keratinocyte apoptosis plays a key pathogenetic role in the formation of eczematous dermatitis. Spongiosis, the histologic hallmark of eczematous dermatitis, is characterized by impairment of cohesion between epidermal keratinocytes. It is conceivable that the intercellular junction of keratinocytes is an early target of apoptosis-inducing T cells. In this study, we demonstrate that the induction of keratinocyte apoptosis is accompanied by a rapid cleavage of E-cadherin and loss of coimmunoprecipitated β-catenin. In situ examination of E-cadherin expression and cellular distribution in acute eczematous dermatitis revealed a reduction in keratinocyte membrane E-cadherin in areas of spongiosis. In contrast, the in vitro and in vivo expression of desmosomal cadherins during early apoptosis remained unchanged. Therefore, induction of keratinocyte apoptosis by skin-infiltrating T cells, subseqent cleavage of E-cadherin, and resisting desmosomal cadherins suggests a mechanism for spongiosis formation in eczematous dermatitis.