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Existing methods for detecting complete virus particles in the serum of patients with chronic HBV infection are either insensitive or indirect. A method is described in which Dane particle-associated DNA is extracted from a small volume of serum and detected by molecular hybridization using 32P-labeled cloned HBV-DNA or HBV-DNA extracted from the serum of an immunosuppressed patient, followed by autoradiography and densitometry. There was a positive correlation between the amount of HBV-DNA detected using HBV particle-derived and cloned HBV-DNA probes. The amount of HBV-DNA detected in serum samples showed a positive correlation with the HBV-DNA polymerase. The method was more sensitive than the DNA polymerase and HBeAg assays in detecting complete virus particles. It may be useful in determining the level of infectivity in patients and in monitoring response to antiviral therapy.