||Bilayer floating-bioadhesive drug delivery systems exhibiting a unique combination of floatation and bioadhesion to prolong gastric residence time were developed. Hydroxypropyl methylcellulose and sodium bicarbonate were added such that when immersed in 0.1N HCl, the tablet expands and rises to the surface and famotidine is gradually released without interference from gas bubbles. Effect of different ratios of drug: polymer on in vitro release profile was investigated. Developed tablets were evaluated for uniformity of weight, hardness, friability, drug content, buoyancy and floating lag time. Time buoyancy curve, detachment force and swelling index were evaluated. Antiulcer activity of famotidine tablets was assessed by inducing ulcers in fasted rats by ethanol and indomethacin. Measurement of gastric contents was carried out by ulcer induced pylorus liagated rats. Prepared tablets exhibited satisfactory physico-chemical characteristics. The tablet swelled radially and axially during in vitro buoyancy studies. From the buoyancy kinetic curve it was observed that bilayer tablet started floating in less than 10 minutes and remained buoyant for 12h. In vivo antiulcer studies exhibited that developed formulation showed comparable percent inhibition of ulcers to standard in both gastric ulcer models. Gastric pH was significantly reduced showing decreased acid output. Thus floating-bioadhesive systems exhibited independent regulation of buoyancy and drug release and in vivo studies showed good antiulcer efficacy confirming potential of floating-bioadhesive tablets as drug delivery system for prolonging gastric residence and enhancing local effect of famotidine.