Lamivudine is a novel 2′,3′-dideoxy cytosine analogue that has potent inhibitory effects on hepatitis B virus replication in vitro and in vivo. We performed a single-blind, placebo-controlled study to assess its effectiveness and safety in Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg carriers were randomized to receive placebo (6 patients) or lamivudine orally in dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug was given for 4 weeks. The patients were closely monitored clinically, biochemically, and serologically up to 4 weeks after drug treatment. All 36 patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA values returned to pretreatment levels within 4 weeks of cessation of therapy. There was no change in the hepatitis B e antigen status or in aminotransferase levels. No serious adverse events were observed. In conclusion, a 4-week course of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg carriers. The suppression was >90% but reversible. Studies with long-term lamivudine administration should be performed to determine if prolonged suppression of HBV DNA can be achieved.