The pharmacokinetics and relative systemic availability or oral propranolol were studied in three healthy volunteers following administration of 10, 40, and 80 mg of propranolol hydrochloride. Plasma concentrations of propranolol were determined using a sensitive and specific fluorometric high pressure liquid chromatographic technique. In the dosage range studied, the amount of propranolol reaching the systemic circulation increased with dose, while half-lives remained unchanged. The apparent 'threshold dose' for propranolol was much smaller than previously reported, and its contribution to the observed dose-dependent availability is doubtful. Apparent intrinsic clearance values were shown to decrease with increase in dose, with a true maximal intrinsic clearance of 5.4 l kg-1 h-1. These data suggest the saturation of a low capacity enzyme system in the liver and are consistent with theoretical characteristics of a drug that is extensively metabolized during its first pass through the liver.