Three groups of calves were inoculated intranasally with infectious bovine rhinotracheitis (IBR) virus, to determine any effects of a 3-day fast on virus replication and interferon (IFN) production measured in nasal secretions (NS). One group ("fasted") was inoculated 24 h after onset of the fast and another ("refed") at the end of fasting, immediately before refeeding. A third ("control") group was inoculated but not fasted. In fasted calves, overall mean virus excretion (during the first 5 postinoculation days) did not differ from that in control calves, though average virus excretion was higher on days 3 and 4, 24 and 48 h after refeeding. In refed calves, overall mean virus excretion was lower (p less than 0.05), yet on day 5 these calves secreted two times more IFN than nonfasted calves. Analysis of the overall data (all 5 postinoculation sampling days) showed that fasted calves produced more IFN (p less than 0.05), with IFN titers sometimes exceeding 1000, than either control nonfasted calves or refed calves. We conclude that fasting enhanced the ability of calves to produce IFN, and this did not result from increased IBR virus replication.