Drug–drug interaction between a commercial diclofenac sodium enteric-coated tablet (Voltaren; V) and a ranitidine HCI tablet (Zantac; Z) was evaluated using a dual radiotelemetric technique according to a randomized three-way Latin-Square crossover design balanced for carryover effects. V and Z were given either alone or in combination (Treatment V, Z, V/Z), with a 14-day washout period between treatments. Eighteen fasted subjects swallowed a tethered Heidelberg pH capsule to provide continuous gastric pH. Then the assigned treatment drug and another Heidelberg pH capsule were given simultaneously. The free pH capsule provided information regarding gastric residence time (GRT). Serial blood samples were obtained for up to 12 hr after dosing and drug levels were determined by validated HPLC methods. Treatment effects on AUC, Cmax, Tmax, Tlag, Tmax– Tlag, and T½ were not significant except Cmax, which differed slightly for both V and Z when given in combination as compared to alone. Gastric residence times were 46, 33, and 51 min for Treatments V, Z, and V/Z, respectively. Gastric exposure of the enteric-coated tablet of diclofenac was estimated by pH values obtained from the tethered capsule. Median pH values at 3 and 15 min prior to gastric emptying were 3.8 and 4.9 for the combination treatment versus 2.1 and 2.7 for diclofenac alone. The results of this study indicated that there was minimal drug–drug interaction between diclofenac and ranitidine. The gastric pH range resulting from this study did not influence the oral absorption of enteric-coated diclofenac.