Researchers have raised concerns about the cost of requiring applicants for US National Institutes of Health (NIH) grants to use male and female animals or cells in preclinical research (see J. A. Clayton and F. S. Collins Nature 509, 282–283;2014). But they should also consider the costs of not taking sex into account: these include failed clinical trials, misdiagnosis and inappropriate therapies for women, and omission of fundamental biological principles.

Many researchers are still unfamiliar with the distinction between sex and gender. Gender combines self- and societal perceptions of a person's sex, so applies only to humans. Sex is the biological result of interplay between sex chromosomes and gonadal hormones.

The impact of sex is dynamic, changing throughout lifespan and in response to injury and disease. Ruling out the influence of sex on a particular endpoint will sometimes be as difficult as identifying it. Sex must be evaluated in the context of other variables, such as age, experience, genetics and environment.

Age-appropriate medicine is a well-accepted idea that is reflected in the formation of NIH centres studying ageing and child health. The factor of sex deserves an equally integrative approach.