The use of 19F-NMR as a noninvasive probe to measure directly the pharmacokinetics of drugs at their target (effector) site(s) is illustrated in this article by human studies with 5-fluorouracil (5-FU). This drug, and several of its metabolites, have been measured in vivo in animals and in patients using standard clinical MRI systems. Using a pharmacokinetic imaging approach the parameter that can be measured most readily is the tumoral t(1/2) of 5-FU. Patients whose tumoral t(1/2) of 5-FU is equal to/greater than 20 min are designated as "trappers", and those whose tumoral t(1/2) of 5-FU is less are nontrappers. Trapping of 5-FU in tumors is a necessary, albeit not a sufficient condition, for response. Problems associated with the technical aspects of these measurements have been discussed, as well as how modulators and other agents will affect the tumoral t(1/2) of 5-FU. The rationale for the biological processes underlying the fate of 5-FU in humans has been illustrated with the use of a 12 compartment model, where several of the steps have been discussed and the consequences of their inhibition/stimulation related to the noninvasive studies that can be performed with modulators of the action of 5-FU. These 19F-NMR studies have now been extended to other fluoropyrimidines, some of which are prodrugs of 5-FU, and others where the fluorine atoms are on the ribose ring. These studies also reveal information that has both scientific and clinical significance. The studies presented here illustrate some of the potential and some of the usefulness of 19F-MRS in patient management and in drug development. It is a technique that has proven itself.