Monitoring plasma concentrations of therapeutic drugs presents special problems when these drugs are metabolized to compounds that have pharmacologic activity. This presentation reviews several methods for evaluating the pharmacologic activity of drug metabolites and describes the impact of active drug metabolites on the pharmacokinetic design of dose regimens and on the formulation of guidelines for plasma level interpretation. Lidocaine and monoethylglycinexylidide illustrate the considerations that pertain when both a drug and its active metabolite have similar therapeutic and toxic actions. Procainamide andN-acetylprocainamide exemplify the much more complex situation that arises when a drug and its active metabolite have different pharmacologic activity.