Streptomyces venezuela, a bacterium isolated from mulched soil near Caracas, Venezuela in 1947, was found to secrete an antibiotic active against Gram-positive and Gram-negative organisms, and rickettsiae.1,2 When it was determined that this antibiotic contained 2 molecules of chlorine, the name chloromycetin was proposed. A few months later, a separate report from the University of Illinois described a broad spectrum antibiotic (chloramphenicol) isolated from a different streptomyces; subsequently it proved to be identical to chloromycetin.3 Although chloramphenicol (the generic name) was developed for its antibacterial activity, its first clinical use was as an antirickettsial agent. In Mexico and Bolivia4,5 during the winter of 1947 to 1948, it was dramatically efficacious in patients with typhus. As an antibacterial drug, chloramphenicol was first used in two patients incorrectly thought to have scrub typhus. They were successfully treated with chloramphenicol; later they were proven to have typhoid fever.6 Since its introduction, chloramphenicol has continued to be widely used as an antibacterial and an antirickettsial agent. CHEMISTRY Chloramphenicol is a lipid soluble compound lacking acidic and basic groups that could form salts. As a consequence, the naturally occurring compound is most soluble in organic solvents, and has a maximum solubility in water of only 4 mg/ml.7 This relative insolubility requires large administration volumes which is a disadvantage in neonates and children. In the middle 195Os it was found that a succinate group attached to the drug by an ester linkage produced a marked increase in aqueous solubiity. In vivo, free chloramphenicol was generated by body esterases that hydrolyze the ester bond.