The systemic availability of clomethiazole was assessed by comparing blood levels after intravenous and oral administration. Clomethiazole was rapidly absorbed after oral administration to volunteers, particularly when administered as syrup. The fraction of the given dose that reached the systemic circulation after 1 capsule of clomethiazole (192 mg clomethiazole) was 0.25 +/- 0.18, after 2 capsules (384 mg clomethiazole) 0.38 +/- 0.18, and after 15 ml syrup (480 mg clomethiazole) 0.42 +/- 0.20. The time-blood concentration profiles were consistent with a two-compartment open model and the mean elimination half-lives of 3.6--5.0 hrs. were found for the different formulations and administration routes. Elimination half-lives showed little variation and a mean systemic clearance of 49 ml/min./kg was found for clomethiazole after intravenous administration. Clomethiazole is bound to human plasma proteins (63.4 +/- 1.6%, 37 degrees), a binding which is not affected by Vacutainer sample tubes. The blood/plasma distribution of clomethiazole was 0.76 +/- 0.02 at 37 degrees. A sensitive mass fragmentographic assay for the determination of clomethiazole in blood/plasma down to levels of 1 ng/ml (6.2 nmol/l) is described.