A simple and rapid method based on derivative spectroscopy has been proposed for simultaneous estimation of Lamivudine and Zidovudine in multicomponent formulations. Each drug is estimated at wavelengths where other show zero amplitude in first derivative spectra. The condition of derivatization was optimized. Proper selections of wavelengths eliminate complex interference raised in estimation of one drug by other. The results of analysis have been validated statistically at a 95 percent confidence level with student's t test and by recovery studies. No interference was observed from common excipients.