Liver biopsies from five patients with chronic non-A, non-B (NANB) hepatitis were examined by electron microscopy for hepatocellular alterations. Circular fused membranes were observed within the cytoplasm of hepatocytes of four of the patients. Aggregates of intranuclear particles, measuring 22 +/- 2 nm in diameter, were also seen in two of the biopsies in which fused membranes were identified. Sera of all five patients formed precipitin lines detectable by counterimmunoelectrophoresis when reacted with serum from an individual convalescent from posttransfusion NANB hepatitis. Using this convalescent serum as an antibody source, complexes of 22 +/- 2 nm particles were identified in three of the chronic patient sera by immunoelectron microscopy. These observations suggest that at last one of the agents responsible for NANB hepatitis elicits both nuclear and cytoplasmic modifications. Furthermore, the 22 +/- 2 nm particles circulating in the sera of the chronic NANB patients may represent components related to NANB hepatitis agent.