Steady-state pharmacokinetics of trazodone were investigated over a period of 4 weeks in seven psychiatric patients after repeated oral administrations of 50, 100, and 150 mg twice daily for one, one, and two consecutive weeks, respectively. Unchanged trazodone was determined by high performance liquid chromatography after a basic extraction. A steady-state level of serum trazodone was achieved for the 50 mg dose within 36 hr, while a new steady state level after increasing the dose to 100 mg and then 150 mg twice daily apparently was achieved at 12 hr. Trazodone showed linear pharmacokinetics within the dosage range investigated. The following main parameters were calculated at steady state for psychiatric patients (mean +/- S.D.): t 1/2 = 7.0 +/- 1.2, V beta/F = 0.50 +/- 0.13 l/kg and Clt/F = 3.2 +/- 0.5 l/hr. These pharmacokinetic parameters did not differ significantly from those earlier reported in healthy subjects after a single dose administration of 100 mg when based on an oral availability of trazodone of 65%.