Plasma kinetics of pipotiazine, a phenothiazine neuroleptic, have been studied in five chronic schizophrenic patients after both oral (25 mg) and i.v. (5 mg) administration of pipotiazine tritiated in the 3- and 4-positions of the piperidine ring. Peak plasma concentrations of unchanged pipotiazine were reached between 1 and 2 h after oral administration and showed a five-fold inter-individual variation. The mean terminal elimination half-life was 11.2 h. After i.v. administration plasma concentration declined bi-exponentially with mean half-life values of 2.7 and 8.8 h. Data indicate that biotranformation of the drug was not dependent on the route of administration and that there were no qualitative differences in biotransformation between individuals. The large apparent distribution volumes (mean value 545 l) indicated extensive binding to tissue components. After 25 mg p.o. effect on the handwriting area was manifest from 8 to 48 h after administration and reached maximum intensity between 24 and 36 h. This is consistent with rather a large duration of action observed clinically.