Evaluation of the biochemical fate of nicotinic acid and the pharmacologic responses it produces illustrate the following general principles. 1. Systemic bioavailability as judged by systemic blood and urine levels of a parent drug may not reflect its bioavailability at the liver, a frequent site of important drug action. 2. Since different pharmacologic effects can show different timedose and route-dose responses, and different degrees of tolerance to repeated doses of the same drug, caution is necessary in evaluating pharmaceutical preparations and making dosage recommendations solely on the basis of drug levels and drug metabolism data. 3. Pharmacologic effects requiring large doses might possibly reflect a need for prolonged exposure rather than high levels. In regard to nicotinic acid itself, the preferred hypocholisterolemic preparation for prolonged treatment may be one which yields little or no discernible blood levels of the drug, in contrast to the vascular effects which require rising nicotinic acid levels, and the fibrinolytic effect which requires parenteral dosage and to which tolerance is acutely developed.