Colostrum-deprived neonate piglets challenged with rotavirus and 3-week-old newly weaned piglets naturally exposed to rotavirus were treated with low doses of natural human interferon alpha (nHuIFN alpha) administered into the oral cavity or included in the liquid diet. The colostrum-deprived piglets given the highest dosage of nHuIFN alpha (50 IU/kg body weight) had lower viral excretion scores at 3 (p less than 0.11) and 4 days (p less than 0.001) after virus inoculation. Average group weights and weight gains were consistently greater for all nHuIFN alpha-treated neonate groups; however, these differences were not significant. Mortality rates were lower in neonates for the three highest nHuIFN alpha treatment groups (20%, 30%, and 20%) than in the lowest treatment group and controls (60% and 45%, respectively). Three-week-old weanling piglets did not have significant differences in the total average diarrhea or rotavirus excretion scores. After 10 days, the group receiving the highest dosage of nHuIFN alpha had significantly greater average weight gain than the control group (p less than 0.05). There was a significant (p less than 0.01) dose-dependent effect between the logarithm10 of the nHuIFN alpha dosage and weight gain in weanling piglets. There were no death losses in the 3-week-old weanling piglets from natural rotavirus exposure.