Cross-adaptation has been interpreted as a measure of the degree to which odors share common sensory channels. How structural similarity, in the absence of perceptual similarity, influences cross-adaptation is unknown. The present study assessed cross-adaptation by structurally similar, but perceptually different, odorants. Magnitude estimates for a 10:1 mixture of (E)- and (Z)-3-methyl-2-hexenoic acid (3M2H), a principal component of human underarm odor, decreased following adaptation to a mixture of (E)- and (Z)-ethyl esters of 3M2H (EE3M2H), which possess a pleasant, fruity odor. Cross-adaptation was asymmetric; adaptation to 3M2H did not significantly affect the perceived intensity of EE3M2H. By contrast, there was no significant cross-adaptation between 3M2H and the fruity-smelling ethyl esters of its homologues, 3-methyl-2-octenoic acid (EE3M20) and 3-methyl-2-pentenoic acid (EE3M2P). Similarity ratings revealed no differences among the three ethyl esters in their perceptual similarity to 3M2H (i.e. all were rated equally dissimilar to 3M2H). Molecular modeling studies revealed no difference in the charge distribution of these molecules. Rather, differences in the shape and size of the hydrophobic part of the molecule may determine the extent of cross-adaptation. These results demonstrate that structurally-similar, yet perceptually-distinct, odorants may cross-adapt and suggest that the extent of cross-adaptation may be affected by the degree of structural, as well as perceptual, similarity.