The bioavailability of two rilmenidine tablet formulations was compared in healthy male (17) and female (8) subjects, aged 18 to 36 years, during a laboratory-blind, randomized, two-treatment, two-period, cross-over study under fasting conditions. In each treatment phase subjects received a single dose of 1.544 mg rilmenidine dihydrogen phosphate (CAS 85409-38-7), equivalent to 1 mg rilmenidine (CAS 54187-04-1). Consecutive dosing was separated by a drug-free wash-out period of 7 d. Following each dosing, serial venous blood samples were collected over a period of 48 h for the determination of plasma rilmenidine concentrations by means of a validated LCMS/MS method. The most frequently reported drug-related adverse events were dizziness and headache ranging from mild to moderate in intensity. The geometric mean C(max) of rilmenidine for the reference and test products was 3.73 and 3.97 ng/ml, respectively. The corresponding geometric mean AUC(0-infinity)) was 34.0 and 35.1 ng x h/ml. T(max) for both products under investigation appeared at 1.33 h. The test product was shown to be bioequivalent to the reference product with respect to all pharmacokinetic variables investigated.