We recently reported on an experimentally induced model of IgA nephropathy in mice by long-term oral immunization under the reticuloendothelial dysfunction, which was found to be effectively inhibited by the administration of the antiallergic agent sodium cromoglycate (SCG). On the basis of these findings, we investigated the participation of food antigens in patients with IgA nephropathy. We studied 24 patients with IgA nephropathy, 11 patients with primary glomerulonephritis (PGN) except IgA nephropathy and 11 healthy controls. Serum levels of immunoglobulins (IgG, IgA, IgE) and circulating immune complexes containing IgG (IgG-CIC) or IgA (IgA-CIC) were measured in the fasting state and 30,60,120 or 180 min after oral challenging with cow’s milk (400 ml). After the oral challenge IgA-CIC levels remained within the normal range in healthy controls and in patients with PGN, while 3 out of the 24 patients with IgA nephropathy showed a transient elevation and 2 cases showed a significant rise of IgA-CIC levels. The levels of IgG, IgA, IgE and IgG-CIC remained uninfluenced by the challenge test in all subjects. In addition, we carried out the same challenge test under SCG administration. These cases indicating an oral-challenge-induced IgA-CIC elevation demonstrated an inhibition of this elevation, and in 3 out 7 patients who showed hyper-IgA-CIC-emia before and after oral challenge IgA-CIC levels returned to the normal range through SCG administration. These results suggest that food antigens participate strongly in the pathogenesis of some patients with IgA nephropathy, and that SCG is an effective agent for such patients.