We have previously shown that adult C57BL/6 mice are relatively resistant to intraperitoneal (i.p.) infection with herpes simplex virus type 1 (HSV-1). Here we show that newborn mice of the strain C57BL/6 are highly susceptible to i.p. infection with HSV-1. Newborn C57BL/6 mice, in contrast to adult mice, did not develop natural killer cell activity in the peritoneal cavity 24 h after i.p injection of HSV-1, and showed only minimal titres of interferon in the peritoneal fluid after 4 h. After 24 h the peritoneal fluid of newborn mice contained high amounts of interferon and high titres of HSV-1. In contrast, the virus titres in the peritoneal cavity of adult mice were significantly lower. It is suggested that the early titres of interferon at the infection site that are observed in adult, resistant C57BL/6 mice but not in susceptible, newborn mice play a decisive role in resistance.