The infectious particles of plaque-derived, low multiplicity passaged wild-type VSV of New Jersey origin consistently induce about 1800 units of interferon (IFN)/10(7) aged chick embryo cells. This inducing capacity is sensitive to both uv radiation and heat (50 degrees). Virus obtained after two successive high multiplicity passages in GMK-Vero cells consistently induced over 25,000 units of IFN/10(7) cells. The IFN induction dose-response curve showed that one IFN-inducing particle (IFP) per cell sufficed to produce a quantum yield of IFN, but infection with two or more IFPs led initially to a marked suppression in the yield of IFN. IFN induction was attributed to two distinct defective particles that differed in size, both containing snap-back RNA, i.e., covalently linked, self-complementary [+/-]RNA. The IFN-inducing capacity of these defective-interfering particles was not inactivated by uv or heat. However heat did eliminate the IFN suppressing activity observed at higher multiplicities, implicating a heat-sensitive component in the virion as a regulator of IFN yield, and involving possibly the virion transcriptase and 3'-leader RNA product.