Caracemide is a nonspecific inhibitor of macromolecules affecting the synthesis of DNA, RNA, and proteins. Caracemide is an active inhibitor of ribonucleotide reductase as evidenced in the Novikoff tumor model. These inhibitory effects are concentration-dependent with 70 percent of DNA synthesis inhibited by a drug concentration of 1 mkM with a 4 h incubation. However, RNA and protein synthesis inhibition require a concentration of 50-100 mkM. DNA strand breaks were observed only at high in vivo concentrations of 100 mkM. The antineoplastic activity of caracemide was observed in the P388 murine model and in mammary (MX-I) and colon (CX-1) human tumor xenographs implanted in the subrenal capsules of athymic mice. In the MX-1 mammary tumor, a single daily injection provided greater activity than an intermittent schedule. Caracemide was inactive against murine L1210 leukemia, B16 melanoma, Lewis lung carcinoma, CD8FI mammary carcinoma and Colon 38. The toxicity on phase I studies was frequent but generally mild. Of note, significant central nervous system dysfunction manifested by lethargy, depression, and confusion occurred in some and was not predictable. In phase I studies Caracemide failed to demonstrate efficacy in patients with advanced renal cell cancer and advanced large bowel cancer.