We have been exploring the potential antiviral efficacy of a class of fluoropyrimidine nucleoside analogues. Initially we explored the drug FIAC for inibition of CMV infection in AIDS patients. Antiviral activity was not seen at tolerated doses and studies turned to this drug's metabolic derivative, FIAU. Studies showed intolerance at high doses but excellent tolerance and profound inhibitory activity at lower doses against hepatitis B virus (HBV). The initial studies involved HIV positive patients with co-existing chronic HBV infection. Profound and even permanent reductions in circulating HBV DNA and antigens was achieved with oral FIAU at daily doses of 0.1, 0.5, or 1 mg/kg for 14 days. Recently, we turned to a broader dose modification study in normal patients with chronic HBV infection. Studies are comparing antiviral efficacy at .05, 0.1, 0.25 and 0.5 mg/kg per day for 28 days. Initial results suggest profound inhibition of HBV infection at the lowest doses and in the absence of any detectible side effects. In the coming year, these studies will be extended to exploit these remarkable results.