We studied absorption of the potentially allergenic protein beta-lactoglobulin during acute rotavirus diarrhea in infants and assessed the relationship of this macromolecular absorption with intestinal sugar permeability. After oral rehydration, 38 patients with acute gastroenteritis were given orally a 100-ml solution containing 4 g (11.7 mmol/L) of lactulose and 0.8 g (4.4 mmol/L) of mannitol, and their recovery rate as shown in urine passed during the subsequent 5 h was measured. A blood sample was taken 2 h after a milk feed for ELISA measurement of beta-lactoglobulin in circulating immune complexes. Twelve nondiarrhea patients were studied after an overnight fast as controls. Immune complexes containing beta-lactoglobulin were found in the serum of all, but the levels [median (range)] were significantly higher in patients with rotavirus diarrhea [686 (36-4352)] than in nondiarrhea patients [165 (0-2594)]; p = 0.007. The mean (95% confidence interval) lactulose/mannitol urinary recovery ratios were increased in patients with acute diarrhea [0.19 (0.10, 0.30)] compared to nondiarrhea patients [0.01 (0.005, 0.02)]; p = 0.0001. Thus, a significant correlation between beta-lactoglobulin absorption and sugar permeability was found; Spearman's rank correlation coefficient = 0.42, p = 0.004. This correlation was not, however, direct but was due to an inverse relationship between urinary recovery of mannitol and serum beta-lactoglobulin immune complexes. These results indicate that rotavirus gastroenteritis is associated with enhanced beta-lactoglobulin absorption and elevated lactulose/mannitol permeability test results, but these represent different phenomena.