It has been proposed that a down-regulation of interleukin (IL)-12 and interferon (IFN)-gamma might be related to susceptibility to allergy in early life. The aim of this study was to assess serum IL-12 levels in food-sensitized and pollen-sensitized children and to compare these with another activation marker, sCD30. Twenty children with pollen allergy and 22 food-sensitized children were included. The diagnosis of immunoglobulin (Ig)-E-mediated allergy, suggested by clinical symptoms, was based on skin-prick tests, serum IgE antibodies and total IgE levels. Samples from 24 non-allergic children were used as controls. IL-12 and sCD30 levels were measured by ELISA. It was found that pollen-sensitized patients had normal IL-12 and higher sCD30 levels than controls (114 vs. 63 U/ml, p = 0.028), but, surprisingly, food-sensitized infants showed normal sCD30 and increased serum IL-12 levels (323 vs. 118 pg/ml, p = 0.0001). No differences were found in patients suffering from asthma or allergic dermatitis. Levels of sCD30 and IL-12 determined in May showed a strong correlation with those obtained in November. Interleukin-12 and IgE levels had an inverse correlation (r = -0.494, p = 0.0001) whereas no correlation was found between sCD30 and IgE. Age had a strong negative influence on IL-12 levels in allergic (Z = 4.834, p < 0.0005) and in normal children (Z = 3.00, p < 0.002); by contrast, sCD30 levels were not significantly age-dependent. When IL-12 levels from the food-allergy group were compared with those from normal controls younger than 4 years of age, the difference remained significant (p = 0.001), ruling out an age-bias. The conclusions made in this study were that serum IL-12 and sCD30 showed different behaviors in children with food or pollen allergy. We found IL-12 and sCD30 levels in pollen-allergic patients that agree with the classical T-helper (Th) 1/Th2 paradigm of allergy. In contrast, serum IL-12 levels were increased in food-sensitized children, suggesting a different immunologic pathogenesis.