The lankacidin-group (T-2636) antibiotics, neutral seventeen-membered macrocyclic antibiotics, are mainly active against Gram-positive bacteria. Chemical modifications of certain functions of lankacidin C has provided a group of lankacidin C analogs and derivatives. These new antibiotics were examined for their in vitro antimicrobial activities, their therapeutic effects against experimental infections in mice, and for their acute toxicities in mice and subacute toxicities in rats. Some of the lankacidin C mono-esters were found to be superior in their biological properties to the parent antibiotic. Among these antibiotics, lankacidin C shows the strongest antimicrobial activities in vitro against Gram-positive bacteria, mycoplasma, Neisseria gonorrhoeae, Vibrio cholerae, Xanthomonas oryzae and clinically isolated staphylococci. Lankacidins A and C administered orally show strong protective effect in mice infected with Staphylococcus aureus 308 A-l (intraperitoneal infection). Lankacidins A and C are low toxic substances in acute toxicity but show a slight depression of body weight gain in the experiments of rat subacute toxicity. This paper deals with the synthesis and biological evaluation of lankacidin C derivatives. These derivatives were prepared with the aim of obtaining more effective derivatives with decreased toxicity.