A rapid reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous assay of theophylline, ephedrine hydrochloride, and phenobarbital in a tablet matrix. A methanolic extract of the powdered sample containing salicylamide as the internal standard was injected into the chromatograph. The HPLC system used methanol-0.007 M monobasic potassium phosphate (37:63, pH 2.3) as the mobile phase. Detection was at 254 nm, and quantitation was based on the drug-internal standard peak area ratio. This ratio was linear over a concentration range of 20.9-83.5 microgram of theophylline, 4-15.9 microgram of ephedrine hydrochloride, and 1.3-5.1 microgram of phenobarbital. Overall recoveries (+/- SD) from three synthetic tablets were: theophylline, 99.8 +/- 1.3%; ephedrine hydrochloride, 100.2 +/- 0.6%; and phenobarbital, 99.4 +/- 0.7%. The method was compared to the compendial method and also was applied to the assay of commercial tablets containing these three active ingredients. The proposed method is applicable to the assay of individual tablets.