The aim of this study was to determine the inhibitory effect of clinically usable proteinase inhibitors p-aminomethylbenzoic acid (PAMBA), and aprotinin on acantholysis in skin organ culture and in clinical trials with pemphigus patients. PAMBA added to the culture medium at a concentration of 1 mg/ml fully prevented the acantholysis, while Contrykal at 10 ATrE/ml reduced acantholysis. Subsequently, we treated 12 patients (groups 1) with PAMBA 100-200 mg daily for 7 to 26 days in combination with a moderate dose of corticosteroid (mean dose 36.1 mg prednisolone equivalent) or immunosuppressive drugs. A second group of 12 patients (group 2) were treated with a high dose of corticosteroid (mean 94.2 mg prednisolone equivalent) and immunosuppressive drugs. Evaluation was performed before treatment, after 3 weeks and on discharge using a clinical scoring system. The inclusion of PAMBA in the treatment protocol of group 1 resulted in active disease being brought under control with lower corticosteroid doses. As a result, fewer side effects were observed in group 1 than in group 2. In our opinion, protease inhibitors may be useful as adjuvant drugs in the combination therapy of pemphigus.