The effects of increased plasma histamine (Hi) on plasma tele-methylhistamine (MeHi) levels and the kinetics of Hi and MeHi elimination from plasma were studied in the cat. Hi (40 or 50 micrograms/kg) was injected intravenously and then Hi and MeHi were assayed by HPLC. Hi injection was followed by a significant increase in plasma MeHi levels, being maximal at 2-4 min. In most animals, maximal MeHi levels exceeded Hi itself. The half-lives (t1/2) of injected Hi were 0.6 and 13.3 min (mean values) in the alpha- and beta-phases, while the corresponding values for MeHi were 1.1 and 15.4 min. The t1/2 of exogenous MeHi (64 micrograms/kg, i.v.) was in the same range. Inhibitors of histamine-N-methyltransferase diminished the elimination rate of both amines studied. Plasma MeHi can thus serve as a marker for increased plasma Hi in the cat particularly because of its noticeable and delayed elevation after the rise in Hi itself.