Sustained release (SR) matrix tablets of dextromethorphan hydrobromide were prepared by wet granulation using hydroxypropyl methyl cellulose (HPMC-K-100 CR) as the hydrophilic rate controlling polymer. The effect of the concentration of the polymer and different fillers on the in vitro drug release rate was studied. The studies indicated that the drug release can be modulated by varying the concentration of the polymer and the fillers. A complete cross-over bioavailability study of the optimized formulation of the developed sustained tablets and marketed immediate release tablets was performed on six healthy male volunteers. The extent of absorption of drug from the SR tablets was significantly higher than that for the marketed dextromethorphan hydrobromide tablet because of lower elimination rate and longer half-life.