A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of H2-receptor antagonists: cimetidine, famotidine, nizatidine and ranitidine hydrochloride. The method was based on the oxidation of these drugs with cerium(IV) in presence of perchloric acid and subsequent measurement of the excess Ce(IV) by its reaction with p-dimethylaminobenzaldehyde to give a red colored product (λmax at 464nm). The decrease in the absorption intensity of the colored product (ΔA), due to the presence of the drug was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990–0.9994) were found between ΔA values and the concentrations of the drugs in a concentration range of 1–20μgml−1. The assay limits of detection and quantitation were 0.18–0.60 and 0.54–1.53μgml−1, respectively. The method was validated, in terms of accuracy, precision, ruggedness and robustness; the results were satisfactory. The proposed method was successfully applied to the determination of the investigated drugs in pure and pharmaceutical dosage forms (recovery was 98.3–102.6±0.57–1.90%) without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.