This study reports the findings of an electron microscopic search for so-called non-A, non-B nuclear particles in liver biopsies from patients with mainly chronic or prolonged liver disease and from chimpanzees. In patients without hepatitis B virus or acute hepatitis A virus serological markers, non-A, non-B-like nuclear particles were seen in hepatocytes in 28 of 31 cases of presumed non-A, non-B hepatitis, but also in 11 of 12 cases of liver disease not usually attributed to hepatitis viruses. They were also seen in 22 of 24 patients with HBsAg, in 3 of 3 patients with anti-HBc and no HBsAg, in 1 of 2 patients with hepatitis A, in a case of cytomegalovirus hepatitis, and in 16 of 19 patients whose serology was not available or inconclusive. The particles were present in 1 of 8 untreated HBsAg-negative chimpanzees and in 2 of 2 HBsAg-positive chimpanzees. They appeared in 4 of 4 chimpanzees developing non-A, non-B hepatitis following exposure to various inocula. Three patterns of particle aggregates were distinguished, all of which had been shown by others in non-A, non-B hepatitis. Dense aggregates were predominant, while others have shown intermediate aggregates more often; reasons for this difference could be technical. No pattern was specific for any condition. Either non-A, non-B-like nuclear particles, although associated with non-A, non-B hepatitis, are not specific for this condition, or non-A, non-B hepatitis viruses are extremely more common than is currently appreciated.