AbstractIn malignant cells the amino groups of cellular proteins are alkylated by homocysteine thiolactone, forming homocysteinyl peptide bonds. In nonnal cells the sulfur atom of homocysteine thiolactone is converted to homocysteic acid, phosphoadenosine phosphosulfate, and sulfate ester. N-substituted derivatives of homocysteine thiolactone synthesized from arachidonic acid, pyridoxal, and maleimide were previously found to have antineoplastic activity. Another N-substituted derivative, the rhodium trichloride complex of oxalyl homocysteine thiolactone, was synthesized and tested for antineoplastic activity. Mice with transplanted rhabdomyosarcoma were injected with solutions of the complex dissolved in lipids. Doses of 50 and 100 mg/kg per day for two weeks produced 50% inhibition of tumor growth. At doses of 100 and 200 mg/kg per day in tumor-free inice there was decreased survival, peritoneal reaction, pigment deposition in lung, jibrocalcijc pericarditis, and leiomyosarcoma of colon (in one animal). The conclusion is that the complex of rhodium trichloride and oxalyl homocysteine thiolactone possesses antineoplastic activity.