The chronopharmacokinetics of indomethacin was studied in patients with rheumatoid diseases after a single oral dose of a new prolonged-release form containing indomethacin 75 mg. The drug was given either at 8, 12 or 20 h and its plasma concentrations, as well as those of its main metabolite, O-desmethyl indomethacin, were followed using a new specific gas chromatographic assay. When given at 20 h plasma indomethacin concentrations did not exhibit a sharp peak and remained much more stable than when the drug was given at 8 or 12 h. In addition, plasma O-desmethyl indomethacin was significantly higher after administration of indomethacin at 20 h than at 8 or 12 h. It is concluded that the pharmacokinetics of the oral prolonged-release form of indomethacin exhibited chronobiological variation. The data are in accordance with clinical studies which suggest that it might be worthwhile to administer this formulation of indomethacin at 20 h.