Evidences supporting the introduction of metallic elements in several biological processes are rapidly accumulating. Likewise, many drugs possess modified toxicological and pharmacological properties when in the form of metal complexes. In order to ascertain the role of various essential and trace element complexation on the antibacterial activity of various cephalosporins, the synergistic or antagonistic behavior of cefadroxil, cephalexin, cefatrizine and cefpirome in presence of essential and trace elements has been studied and compared with the parent drug. The essential and trace elements comprised of magnesium, calcium, chromium, manganese, ferric, cobalt, nickel, copper, zinc and cadmium in the form of their chloride. These studies were carried out by observing the minimum inhibitory concentration (MIC) using agar dilution method and compared with the MIC'S of the standard cephalosporins against various species of Gram (+) and Gram (-) microorganisms such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhi and Shigella dysenteriae. Different dilutions of cephalosporins and salts of essential and trace elements were used in these studies. The ratio of the drug and metal salts was 1:1 and the reactions were carried out at two different temperatures as 37 degrees C and 60 degrees C in order to study the complex formation. The aim of our study was on one hand to evaluate the changes in microbiological activity of the standard cephalosporins after in vitro metal interactions to study the synergetic or antagonistic behavior of the later through the difference in MICs values of these cephalosporins and on the other hand to access the bioassay directed extent of drug metal complexations. Our investigation reveal that interaction of above cephalosporins with essential and trace elements cause antagonistic effect in many cases which was shown by decrease in antimicrobial activity of cephalosporins and MIC values were increased.