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Background Human milk contains a 46 kDa mucin-associated glycoprotein, lactadherin, which binds specifically to rotavirus and inhibits its replication. This study tested the hypothesis that lactadherin protects against symptoms of rotavirus infection.Methods 200 infants in Mexico City were recruited at birth and monitored by regular stool EIA for rotavirus, serology, and recording of feeding and stool patterns.Milk samples were obtained from the mothers weekly until 4 weeks post partum then monthly. The sample taken immediately before an infant's episode of rotavirus infection was assayed for lactadherin, butyrophilin, mucin, and secretory IgA. An infection was defined as symptomatic if diarrhoea occurred in the 5 days before or after detection of the virus.Findings 31 infants developed rotavirus infection; 15 were symptomatic and 16 had no symptoms.The median concentration of lactadherin in the milk samples (obtained 4-41 days [median 13] before the infection) was 48.4 (range 5.6-180) microgram/mL in the asymptomatic group and 29.2 (6.2-103.4) microgram/mL in the symptomatic group. Although these medians did not differ significantly, in logistic regression analysis adjusted for age at infection and secretory IgA concentration there was a significant difference between the groups (p=0.01). No association between symptom status and concentrations of butyrophilin, mucin, or secretory IgA was found.Interpretation Protection against rotavirus by human milk is associated with the glycoprotein lactadherin.This association is independent of products of the secretory immune system.