To establish if intestinal permeability to exogenous antigens is involved in cow's milk allergy (CMA) in infants, 33 children 1 to 24 months old (18 controls and 15 with CMA) were tested for intestinal permeability to the protein marker horseradish peroxidase (HRP). Jejunal biopsies were performed either during the initial period of diagnosis, at the mean (and SE) age of 3 +/- 1 months, and/or 1 yr later, at the age of 13 +/- 2 months, just before and after a milk challenge. A small fragment of the biopsy was studied for histology and the remainder was mounted in an Ussing chamber for simultaneous measurement of mucosal to serosal transport of HRP in its intact and degraded forms and electrical parameters including short-circuit current and conductance. No modification in HRP absorption was noted in control children aged from 2 months to 11 yr, indicating that gut closure probably occurred earlier in life. During the initial period of CMA, transepithelial HRP fluxes were significantly higher, about 8-fold, in children with CMA (intact HRP flux = 48.5 +/- 15.2, 95% confidence interval, 11.2 to 85.7 versus 5.9 +/- 1.2, 95% confidence interval 2.9 to 8.3, in control children). In addition, short-circuit current was increased but conductance was unchanged. After several months on a milk-free diet, HRP flux and short-circuit current returned to control values. Just after the milk challenge and independently of the clinical issue, a slight rise in HRP permeability was observed but it was not significant and remained within control values.(ABSTRACT TRUNCATED AT 250 WORDS)