Formulation of famotidine, rapidly disintegrated sublingual tablets, by direct compression was carried out. Fifteen tablets formulae were made in order to obtain suitable non-friable formulae, with disintegration time less than one minute and average crushing strength of 2-4 kg/cm2. The excipients used in the different formulae are Avicel pH101, sorbitol, mannitol, lactose anhydrous, Ac-Di-Sol, magnesium strearate and saccharin sodium. The formulae prepared were tested for the effect of certain excipients on the hardness, friability and disintegration time. Tablets of 20 mg famotidine from the formulated and commercial oral dosage forms were administered to five healthy volunteers participated in the study using a balanced cross-over design. Comparison of the mean urinary excretion rate obtained after administration of both dosage forms indicated that in both cases, the time taken to reach peak occurred at a mid point of 1.5 hours. Comparison of the cumulative amounts excreted in the urine after administration of famotidine in the two different dosage forms revealed that about 5.49±1.06 mg of the administered dose (20 mg) was recovered unchanged in the urine during 12 hours following sublingual tablets administration. This value was found to be higher than that excreted after administration of Pepcid® oral tablets (4.61±0.65 mg) during the same period of time. Statistical analysis of the difference at P= 0.05, revealed non-significant difference in the urinary excretion rate obtained of the two different dosage forms. On the other hand, a significant difference was found to exist in the total cumulative amount of famotidine excreted in the urine at 2 and 6 hours from both dosage forms. The results also indicated that there was no significant difference in AUC0-12 between the two dosage forms.