The practice of internal medicine involves daily exposure to abnormalities of acid-base balance. A wide variety of disease states either predispose patients to develop these conditions or lead to the use of medications that alter renal, gastrointestinal, or pulmonary function and secondarily alter acid-base balance. In addition, primary acid-base disease follows specific forms of renal tubular dysfunction (renal tubular acidosis). We review the acid-base physiologic functions of the kidney and gastrointestinal tract and the current understanding of acid-base pathophysiologic conditions. This includes a review of whole animal and renal tubular physiologic characteristics and a discussion of the current knowledge of the molecular biology of acid-base transport. We stress an approach to diagnosis that relies on knowledge of acid-base physiologic function, and we include discussion of the appropriate treatment of each disorder considered. Finally, we include a discussion of the effects of acidosis and alkalosis on human physiologic functions.