Studies were carried out to develop a simple, rapid and accurate spectrophotometric method for the analysis of fifteen cephalosporins. The method depends on the charge-transfer complexation reaction between any of these drugs as an n-electron donor and p-chloranilic acid (p-CA) as a pi-acceptor to form a violet chromogen measured at 520 nm. Different variables affecting the reaction were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9986-0.9996) were found between the absorbances and the concentrations of the studied drugs in the range of 4-1,200 microg ml(-1). The limits of assay detection ranged from 2.54 to 42.83 microg ml(-1). The accuracy and precision of the method were satisfactory. The method was successfully applied to an analysis of the studied drugs in their pharmaceutical formulations; the recovery percentages ranged from 96.76 +/- 0.87% to 100.50 +/- 1.30%. The interaction sites were confirmed by UV/VIS, IR, 1H-NMR techniques. Molecular modeling for the interaction was used for deriving an equation for calculating the epsilon value for a particular drug. This equation gave a perfect prediction for the degree of interaction of the investigated drugs with the p-CA reagent.