Sera obtained within 7 days after clinical onset of acute hepatitis type B were positive for hepatitis B virus (HBV) DNA by spot hybridization only in 4 out of 45 patients who subsequently recovered, but in 10 out of 10 patients who instead developed chronic infection. These results indicate that in uncomplicated acute hepatitis B, virus replication is limited to an early phase of infection, often preceding the onset of clinical symptoms, and suggest that serum HBV-DNA may represent an early and predictive marker of chronicity.