The successful functioning of oral medication depends primarily on how the gastrointestinal (Gl) tract processes drugs and drug delivery systems. Parameters such as regional pH, motility (and hence residence time), and brush border and colonic microflora enzymatic activity play an important role in the performance of orally administered dosage forms. In addition, medications are required to treat disease states that alter normal functions of the body. This review (which summarizes the symposium of the same title undertaken in the 2nd Jerusalem Conference on Pharmaceutical Sciences and Clinical Pharmacology, Jerusalem, Israel, May 1992) focuses on two aspects: (1) how some physiological parameters of the intestine can be manipulated to achieve control over drug absorption (P. Bass: alteration of the paracellular space of enterocytes with glucose to modulate the passive movement of drugs; E. Ziv: intestinal absorption of insulin) and spatial placement of drugs (D. R. Friend: use of colonic β-glucosidases to target glycoside prodrugs of steroids to the large bowel; A. Rubinstein: specific degradation of polysaccharide matrices by colonic bacteria); and (2) how abnormalities of the Gl tract affect drug performance (J. B. Dressman: physiological and pathophysiological changes in upper Gl tract pH may lead to alterations in drug bioavailability; W. A. Ritschel: influence of diseases on the pharmacokinetics of drugs).