The clinical use of cyclosporine A (CsA) is complicated by large intra- and interindividual variabilities in its pharmacokinetics. Several factors contribute to these variabilities. This review aims at describing these factors and their relative contribution in the clinical situation. Cyclosporine A has a highly variable absorption. The absorption is dependent on the liver function, bile flow, and gastrointestinal status. A large fatty meal may increase the absorption of CsA. Impaired absorption is observed postoperatively. The vehicle or dosage form is of no importance for the absorption. The distribution of CsA is mainly influenced by the lipoprotein concentration in plasma and to a lesser extent by the haematocrit. However, age, gender, and obesity are of no clinical importance for the distribution. The metabolism is presumably genetically determined and the rate of metabolism varies greatly between individuals. Furthermore, the rate of metabolism is age-related and may be affected by concomitant medication. Factors of limited importance for the metabolism include sex, lipoprotein pattern, and drug concentration. Factors such as time after transplantation, haemodialysis, haematocrit, obesity, and uremia are not associated with altered metabolism. Thus, the major factor for the intraindividual variability in CsA kinetics is the variable absorption, whereas the major cause for the interindividual variability supposedly is the inherited capacity to metabolize the drug. The factors mentioned above and other factors, found to be of minor or no importance for the kinetics of CsA, are discussed in detail.