Despite some evidence that genotype-environment interaction (G x E) effects may be involved in the variation observed in behavioral and biological traits, few attempts have been made to detect and quantify this component of genetic variation in humans. We propose that one way to achieve this goal is to challenge several genotypes in a similar manner, submitting both members of several MZ twin pairs to an ethically acceptable experimental treatment capable of inducing an adaptative response. In this situation, the G x E effect can be assessed with a two-way analysis of variance for repeated measures on one factor, the treatment effect. In this design, twins are considered nested within the pair, whereas the treatment effect is considered a fixed variable. The intrapair resemblance in the response to the treatment is quantified with an intraclass correlation coefficient computed with between-sibhips and within-sibhips means of squares. To illustrate this approach, changes induced by long-term endurance training were studied in 10 MZ twin pairs. Significant intrapair resemblance in the response of maximal oxygen uptake was observed, with about 7 to 8 times more variance between pairs than within pairs. This design with MZ twins may be helpful in the study of human variation for multifactorial phenotypes.