Clinical chemistry parameters were investigated in piglets weaned at 22 and 28 days. The effects of an oral, low-dose interferon (IFN)-alpha treatment at weaning were evaluated as well. The trial was carried out on 59 piglets from the same farm, allocated to three groups: the first and the second groups were weaned at 28 and 22 days of age, respectively; the third group was weaned at 22 days and orally treated at weaning with IFN-alpha at a low dose (1 IU human lymphoblastoid IFN-alpha /kg body weight in drinking water) for 10 consecutive days. The results of the field trial confirmed that weaning is one of the main stressing events for pigs at intensive farms. In particular, these findings are based on a dramatic increase in serum haptoglobin levels after weaning in the three groups under study. Results also indicated that early weaning at 22 days implies higher environmental adaptation. In such animals, an oral, low-dose IFN-alpha treatment gave rise to a peculiar, negative, acute-phase response (reduced levels of serum albumin) and to significantly lower alpha-globulin concentrations in sera. Taken together, IFN-alpha was shown to modulate inflammatory responses to early weaning stress.