Two chimpanzees with persistent non‐A, non‐B (NANB) hepatitis were superinfected with marmoset‐passaged MS‐1 HAV. Two control chimpanzees were also infected with marmoset‐passaged HAV. Neither animal with persistent NANB hepatitis developed elevated alanine aminotransferase (ALT) activity, whereas both control chimpanzees exhibited ALT elevations within 3 weeks after inoculation. In addition, both NANB‐infected chimpanzees demonstrated a delayed anti‐HAV antibody response in which one animal failed to produce detectable IgM anti‐HAV. With the exception of one stool, all serial liver biopsy specimens and daily stool suspensions from the superinfected chimpanzees were negative for HAV antigen. One chimpanzee with a chronic HBV infection was superinfected with non‐A, non‐B hepatitis and was shown to develop elevated ALT activity and hepatocyte ultrastructural alterations accompanied by a marked reduction in the titer of serum HBsAg. Our combined findings indicate that acute and persistent non‐A, non‐B hepatitis infections are capable of interferring with two distinctly different hepatotropic viruses. These results also suggest that in vitro detection of non‐A, non‐B hepatitis infection or virus(es) may be achieved by antibody‐independent methodologies that employ the basic principle of viral interference.