Purified diphtheria toxin was administered i.v. to 50 patients with advanced solid tumors. The doses of toxin varied according to the different immunological status of the patients against diphtheria. The prominent toxic effects of the treatment were transient peripheral neuropathy observed in two nonimmune patients and fever (37–41°) which occurred in all immune patients with cell-mediated hypersensitivity to toxin. A partial response lasting from 2 to 4 weeks was achieved in three of 13 nonimmune patients and in one of three nonimmune patients with cell-mediated hypersensitivity. Of 21 immune patients, nine had partial response lasting from 4 to 12 weeks. Of 13 immune patients with cell-mediated hypersensitivity, six had partial and five complete response lasting from 2 to 12 and from 1 to 25+ months, respectively. The overall response rate was 48%. The results suggest that diphtheria toxin may have a role in cancer immunotherapy.