It is estimated that chronic hepatitis B affects to than 350 million people around the world. Patients with AgHB- minus account, in some areas, for between 50-80% of the total of the population with chronic hepatitis B. Spontaneous clearance is rare within these patients, the response to interferon is low and the probability of developing cirrhosis and hepatocarcinoma is higher than in the wild type.To analyze the response to lamivudine treatment in patients with chronic hepatitis B which are AgHB negative.Seven of the 9 patients which were treated in our department for more than 3 months were AgHB negative. Six of them responded to the treatment in an average time of 3.5 months (range 1-6 months). There were two patients that relapsed at 18 and 24 months and they were treated with adefovir. Four patients remained DNA negative and had normal aminotransferases values after an average treatment time of 25 months.In our series, the majority of the patients (77.7%) were AgHB negative at the beginning of treatment. The efficacy of the treatment with lamivudine in these cases is high (85.7%) and with an early response (average 3.5 months). One third of patients treated relapsed after one and a half years of treatment.