Metal ions have been reported to form chelate complexes with certain drug molecules especially those that contain ligand donor atoms. In this study, the in vitro availability of chloramphenicol in the presence of Pb and Cd was evaluated. These studies were carried out in simulated gastric juice (0.1M HCl) and intestinal pH (pH 9) at 37°C over period of 180 minutes. A double scanning UV/VIS spectrophotometer (Helios Zeta, Model 164617) was used to analyze drug content by measuring absorbance at 278 nm. An overall chloramphenicol availability of 89, 88.6 and 86% was achieved in simulated gastric juice for chloramphenicol alone, in the presence of Pb, and of Cd respectively. The corresponding availabilities observed in simulated intestinal pH were 82.5, 63.2 and 63.2%. The presence of Pb and Cd did not significantly affect the overall availability of chloramphenicol in simulated gastric juice. However, the availability of the drug was significantly decreased by Pb and Cd in simulated intestinal pH. The results of this study indicate that the availability of chloramphenicol may be reduced in the presence of Pb and Cd especially from the intestine, which may result in therapeutic failure.