A sensitive and specific reversed phase HPLC method was developed to quantitate plasma levels of cisapride in order to conduct comparative bioavailability studies. The drug and internal standard was extracted from plasma with heptane-isoamyl alcohol (95:5 v/v) and back extracted with sulfuric acid. The acidic layer was then re-extracted with the same extracting solvent. The separated organic layer was evaporated to dryness under nitrogen and the residue reconstituted with acetonitrile. Analysis was performed on a C-8 Sil-X-10 HPLC column, with a mobile phase of acetonitrile, water, and triethylamine (75:25:0.01) and UV detection at 215 nm. The standard curve covering the concentration range 5-160 ng/ml was linear (r(2)=0.9992), relative errors were within +/-10% and the CV% ranged from 1.34 to 11.82. The in vivo study was carried out in 12 healthy volunteers according to a single dose, two-sequence, cross over randomized design. The bioavailability was compared using the total area under the plasma level versus time curve (AUC(0-34,) AUC(0- infinity )), peak plasma concentration (C(max)) and time to C(max) (T(max)). No statistically significant difference was found between the AUC(0- infinity ) or C(max) values of the test (cisapride) and reference (Propulsid). It was, therefore, concluded that the generic cisapride was bioequivalent with the innovator formulation.