A major diphtheria epidemic affecting the whole population of St. Petersburg started in 1990. During the period of 1991 to 1995, 4600 patients with clinical respiratory tract diphtheria were treated in Botkin's Hospital. From 112 (2.4%) of these patients only a nontoxigenic strain of Corynebacterium diphtheriae was isolated. Three patients with this strain who were suffering from clinical disease consistent with classical toxic diphtheria died. All had myocarditis, two had asphyxia due to membrane formation in the lower respiratory tract, and one had severe polyneuritis. In two patients the causative agent was of the biotype mitis and in the third intermedius, whereas the prevailing epidemic strain was of the biotype gravis. As the clinical presentation of the disease in the three patients who died was typical of toxic diphtheria, it is considered likely that the immunodiffusion test for toxin production in vitro may fail to detect strains of Corynebacterium diphtheriae producing toxin in vivo.