The main objective of the present study was to determine the influence of acute deficits of protein and energy on the blood serum level of interferon-γ, a signature type 1 polarising inflammatory cytokine. In two 14 d experiments, male and female C57BL/6J mice, initial age 19 d, consumed a complete purified diet ad libitum or in restricted daily quantities, or had free access to an isoenergetic purified low-protein diet. A zero-time control group (age 19 d) was included in the second experiment. Serum interferon-γ was assessed in both experiments by sandwich ELISA and, in the second experiment, also by a bioassay based on inhibition of proliferation by WEHI-279 B lymphoma cells. The immunoassay detected interferon-γ inconsistently in all groups (range 0–14 pg/ml; detection limits 1–5 and 0–7 pg/ml in experiments 1 and 2, respectively). By contrast, interferon-γ bioactivity was found in all animals of each group (means 339, 499, 124 and 200pg/ml in zero-time controls, age-matched controls, low-protein and restricted intake groups, respectively; detection limit, 12 pg/ml), and the mean serum bioactivity of each malnourished group was low compared with the age-matched control (P≤ 0–05). The present study defines the physiological serum interferon-γ bioactivity of the adolescent mouse. Moreover, to the extent achievable by way of the blood, the results reflect the influence of metabolically diverse forms of acute malnutrition on the polarising type 1 cytokine profile within lymphoid microenvironments wherein immune responses arise. Therefore, the results suggest a mechanism underlying the cell-mediated inflammatory incompetence that characterises acute, prepubescent malnutrition.