A case of necrotizing cellulitis of the penis is reported. In this patient, transient functional protein S deficiency during the infectious process was demonstrated with a marked decrease of free protein S and elevated C4b-binding protein levels. Moreover, by investigating other members of this patient's family it was possible to demonstrate a subclinical inherited protein S deficiency. In this study it is suggested that the profound and transient decrease of functional protein S observed in this patient during infectious cellulitis, may have contributed to the pathogenesis of tissue necrosis. [ABSTRACT FROM AUTHOR]