Macromomycin (MCR) and auromomycin (AUR), a chromophore containing derivatives of MCR, are antibiotic proteins isolated from Streptomyces macromomyceticus. They are reported to be active against tumors in experimental animals with L1210 and P388 leukemias, B16 melanoma, and Lewis-lung sarcoma. AUR is more cytotoxic to MCR in all these studies. Studies on the mechanism of action suggest MCR and AUR to induce inhibition of DNA synthesis, cause DNA strand scissions in vivo in both HeLa and human leukemic (CCRF-CEM) cells. MCR is also reported to be cytotoxic by its interaction with the cell surface receptors like neocarzinostatin (NCS). MCR preparations, obtained commercially or through the National Cancer Institute, appear to be impure and unstable. Procedures for purification of MCR and AUR have been established. Also, AUR has been shown to contain a biologically active chromophore in the purified preparation. Chemical and amino acid analysis of MCR and AUR and understanding of the structural similarities of these two proteins and NCS may help in understanding the need for certain structural requirements in the proteins for induction of cytotoxicity. Preclinical evaluation of the drug in experimental animals would help clinicians in planning Phase I studies. Covalent coupling of these highly toxic proteins to tumor specific monoclonal antibodies would facilitate selective tumor orientation of the drug, thus reducing toxicity to normal cells during chemotherapy.