Contradictory results have been reported on the use of goats' milk in cows' milk allergy. In this study the hypothesis was tested, using a guinea pig model of cows' milk allergy, that these discrepancies could be due to the high genetic polymorphism of goats' milk proteins. Forty guinea pigs were fed over a 20 d period with pelleted diets containing one of the following: soyabean proteins (group S), cows' milk proteins (group CM), goats' milk proteins with high (group GM1) or low (group GM2) αs1-casein content. Parenteral sensitization to GM1 and GM2 proteins was also assessed. The sensitization was measured (1) by systemic IgG1 antibodies directed against bovine or caprine β-lactoglobulin (β-lg), α-lactalbumin (α-la) and whole caseins, and (2) by intestinal anaphylaxis measured in vitro in Ussing chambers, by the rise in short-circuit current (ΔIsc) in response to milk proteins. Guinea pigs fed on CM and GM1 developed high titres (> 1500) of anti-β-lg IgG1, with an important cross reactivity between goat and cow β-lg. However, in guinea pigs fed on GM2, anti-goat β-lg IgG1 antibodies were significantly decreased compared with GM1 guinea pigs (mean IgG1 titres were 546 and 2046 respectively), and the intestinal anaphylaxis was significantly decreased (3·5±4·5 μA/cm2) compared with that observed in GM1 guinea pigs (8·3±7·6 μA/cm2). Animals receiving GM1 or GM2 proteins via the parenteral route developed a marked sensitization. These results suggest that the discrepancies observed in the use of goats' milk in cows' milk allergy could be due, at least in part, to the high genetic polymorphism of goats' milk proteins.