Non-expensive and low-complexity surrogate markers for monitoring the response to combined antiretroviral therapy (combined-ART) are needed in poor-resource settings where routine assessment of CD4+ T-lymphocyte count and viral load can not be afforded. We longitudinally evaluated Ig serum levels in 234 HIV-1 infected children receiving combined-ART with > or = 3 drugs. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using the mean and standard deviation of the normal population for each age period. Data from 17 (7.3%) children with immunological failure and from 54 (23.1%) children with virological failure of combined-ART were compared with data from not-failed children. At baseline children with immunological failure showed higher IgM z-scores (P = 0.042) than children without. After 3-12 months of therapy immunologically failed children displayed higher viral loads (P < 0.0001) and IgA (P = 0.043) z-scores than not-failed children. Similarly, at the same follow-up time, children with virological failure showed lower CD4(+) T-lymphocyte percentages (P = 0.005) and higher IgA z-scores (P < 0.0001) than not-failed children. No difference in IgG or IgM z-scores was evidenced between failed and not-failed children after 3-12 months of therapy. In conclusion, IgA serum level is a cheap and low-complexity marker of immunological or virological failure of combined-ART which might be adopted in poor-resource settings.