Rat and human alpha-fetoproteins, (AFP) were able to bind arachidonic acid with high affinity (Ka = 10(7) to 10(8) M-1). Nevertheless, a great difference was found in the binding capacity of these two proteins. Rat AFP was shown to possess one high affinity binding site and several (12-13) low affinity sites while human AFP presented three equivalent binding sites for polyunsaturated fatty acids. Estrogenic hormones compete with fatty acids bound to the high affinity binding site of rat AFP but remained unable to displace arachidonic acid bound to the human one.