Dehydroepiandrosterone, an adrenal steroid, has many purported roles in the body and has been used as an oral supplement in the treatment of various illnesses. Because little is known about normal changes over time in dehydroepiandrosterone concentrations, we studied the 5-year change in plasma dehydroepiandrosterone concentrations in 614 free-living adults. Two hundred seventy-three males and 341 females had dehydroepiandrosterone and dehydroepiandrosterone sulfate concentrations measured in 1989 and 1994. Demographic data were also obtained. Dehydroepiandrosterone concentrations differed significantly by sex and 5-year age group. The average decline in dehydroepiandrosterone was 5.6%/year, and the rate of decline was directly related to age but not to sex, measures of adiposity, or serum glucose. Dehydroepiandrosterone sulfate concentrations differed significantly by sex and age group. The average decline in the sulfated hormone was 2.0%/year and was not related to age, sex, measures of adiposity, or serum glucose. Knowledge of the natural course of age-related changes in dehydroepiandrosterone and dehydroepiandrosterone sulfate concentrations is essential to our understanding of the relationship of dehydroepiandrosterone to chronic diseases.