The effect of various formulation additives on the dissolution behavior of three tetracycline antibiotics from compressed tablets (prepared by direct compression) was studied. In general, the dissolution of the antibiotics was found to be retarded by the addition of binding agents such as gelatin and acacia, when they were incorporated in compressed tablets. A study was also undertaken to determine the influence of gelatin and acacia dissolved in the test media. In dissolution experiments on compressed tablets and crystalline powders, a significant dissolution inhibition by the action of the dissolved additives was present, as in the study where additives were incorporated in compressed tablets. It was thought that the possible mechanisms for the retardation effect included the formation of a poor soluble complex between the drug and the additives and the increased viscosity of the medium. A blood level study was also conducted in rats using CTC-HCl and TC-HCl as test materials to determine whether gelatin and acacia affect the membrane permeability of drugs from solutions. Blood concentrations after intraduodenal administration of these two drug solutions with gelatin and acacia were compared to each control level produced by the drug given alone. These two additives resulted in lower blood levels compared to control values.