Plasma concentrations of indomethacin have been studied in 5 healthy volunteers after single and multiple doses (25 mg intravenously [iv], 25, 50, and 100 mg orally, 100 mg rectally, and 25 mg three times daily [tid]. In 8 other normal subjects and in 5 patients a 50-mg oral dose of indomethacin was given and the indomethacin concentration was followed from 8 to 32 hr after dosing. All analyses were carried out using a new mass fragmentographic method. After oral and rectal doses the plasma decay of indomethacin was biphasic, and the data were interpreted according to a 2-compartment open model. The half-life of the beta-phase varied between 2.6 and 11.2 hr. The volume of distribution ranged from 0.34 to 1.57 L/kg and the plasma clearance from 0.044 to 0.109 L/kg/hr. There was no evidence of dose-dependent elimination. Indomethacin was rapidly and well absorbed after oral dosing with peak plasma concentrations within 2 hr. Comparison with the area under the curve (AUC) after iv dosing indicated complete bioavailability. The AUC after rectal dosing indicated complete bioavailability, but the rate of absorption was slower than after oral administration. Indomethacin, 25 mg three times daily, was also given for 9 days to the same normal subjects; equilibrium concentrations obtained did not differ significantly (p greater than 0.1) from those predicted from single-dose data in the 5 subjects.