Investigation of blister fluid (BF) from 49 pemphigus vulgaris and 27 bullous pemphigoid patients revealed direct interrelation between proteolytic and cytotoxic activities of BF. Human epidermal keratinocytes proved to be more sensitive to the cytolytic effect of BF as compared to human endotheliocytes and fibroplasts. Epidermal keratinocyte cultivation in patients' BF led to proteolytic activity enhancement in culture supernatant. Inasmuch as cytotoxic and proteolytic activity of BF sharply decreased under the effect of inhibitors of serine proteinases only, it was concluded that proteolytic enzymes of this class play the role of a" cytotoxic factor" causing the lysis of epidermal cells in pemphigus and pemphigoid.