The importance of metabolites as active and toxic entities in drug therapy evokes the need for an examination of metabolite kinetics after drug administration. In the present review, emphasis is placed on single-compartmental characteristics for a drug and its primary metabolites under linear kinetic conditions. The determination of the first-order elimination rate constants for drug and metabolite are also detailed. For any ith primary metabolite mi formed solely in liver, kinetic parameters with respect to primary metabolite formation under first-order conditions require a comparison of the areas under the metabolite concentration-time curve after drug and preformed metabolite administrations. These area ratios hold regardless of the number of noneliminating compartments for the drug and metabolite. These parameters include fmi and gmi, the fractions of total body clearance that respectively furnishes mi to the general circulation and forms mi, and hmi, the fraction of hepatic clearance responsible for the formation of mi. Moreover, the fraction of dose dmi converted to form mi is defined with respect to the route of drug administration. The inherent assumption of these estimates, however, requires that the extent of sequential elimination of the generated mi be identical to the extent of metabolism of preformed mi. Discrepancies have been found, and may be attributed mostly to the uneven distribution of drug-metabolizing activities as well as to the presence of diffusional barriers. Other linear systems that involve mi formation from multiple organs are briefly described.