The action of L-triiodothyronine, L-thyroxine, and their analogues on the (Ca2+ + Mg2+)-ATPase of erythrocytes from rats fed with two different fat-supplemented diets has been studied. It was found that only L-triiodothyronine and L-thyroxine have effects on the (Ca2+ + Mg2+)-ATPase of both groups, producing inhibition in rats fed with corn oil and activation in rats fed with lard-supplemented diets. The half-maximal effect for L-triiodothyronine and L-thyroxine are, respectively, on the order of 10(-10) and 10(-8) M. These changes were not obtained with analogues of the hormones. It is suggested that the response of this enzymatic system to the hormonal action is conditioned by the fatty acid composition of membrane-bound lipids. This observation is novel in the hormonal research area.