Patients with primary squamous cell epitheliomas of the oral cavity, pharynx, and larynx were stratified according to stage and site and randomized to receive either intratumoral immunotherapy with Corynebacterium parvum followed 2 weeks later by surgery and postoperative C parvum for 2 years or surgery alone. There were 209 patients entered into the trial and 176 were fully evaluable. All prognostic variables were similar between the two groups. There was no difference in disease-free survival or absolute survival between the two groups of patients. In addition, there was no difference noted for any stage and/or site. The only difference in sequential immunologic testing was that chemokinesis was increased following intratumoral C parvum, but neither this nor any other immunologic test correlated with ultimate recurrence or survival. These data demonstrate that immunotherapy using preoperative, intralesional C parvum and postoperative, subcutaneous C parvum is ineffective when used as an adjuvant to surgery for primary cancers arising in the oral cavity, pharynx, and larynx.