The aim of this study was to investigate the influence of dissolution medium on the in vitro release of lamivudine (100 mg) from four commercially available lamivudine tablets (one reference and three generic). Three different buffer solutions (pH 1.2, 4.5, 6.8) and deaerated water were used as the dissolution media (900 mL), and the paddle rotation speed was kept at 50 rpm with twelve replicates. An RP HPLC method was developed for analysis of lamivudine in samples obtained from dissolution studies. The mobile phase consisted of acetonitrile/water (10:90) pH adjusted to pH 2.5 with o-phosphoric acid, a C-18 column (Ace 250 x 4.60 mm, 5 mu m) was used, and the flow rate was set at 1 mL/min. All the drugs tested were very rapidly dissolving (more than 85% of the labeled amount in 15 min), and the dissolution profiles of the generic tablets were thus considered similar to that of the reference tablet in each of the buffers at pH 1.2, 4.5, and 6.8, and deaerated water. Because of the dissolution results and the high solubility and borderline permeability, a biowaiver can be proposed for lamivudine immediate-release solid oral dosage forms provided that the excipient composition of the test product is the same as or similar to that of the reference product and the excipients that have an effect on bioavailability are qualitatively and quantitatively the same as that of the reference product.