Despite research and clinical significance, limited information is available on the relations between skeletal muscle (SM) and age in adults, specifically among Hispanics, African Americans (AA), and Asians. The aim was to investigate possible sex and ethnic SM differences in adults over an age range of 60 years. Subjects were 468 male and 1280 female adults (≥18 years). SM was estimated based on DXA-measured appendicular lean-soft tissue using a previously reported prediction equation. Locally weighted regression smoothing lines were fit to examine SM trends and to localize age cutoffs; piecewise multiple linear regression models were then applied, controlling for weight and height, to identify age cutoffs for sex-specific changes in SM among the ethnic groups. The age of 27 years was identified for women and men as the cut-off after which SM starts to show a negative association with age. Both sexes had a similar ethnic pattern for expected mean SM at the age cutoff, with AA presenting the highest SM values, followed by Whites, Hispanics, and Asians. After the age cutoffs, the lowering of SM differed by ethnicity and sex: AA women showed the greatest SM lowering whereas Hispanic women had the least. Hispanic men tended to show a higher negative association of SM with age followed by AA and Whites. To conclude, significant sex and ethnic differences exist in the magnitude of negative associations of SM with age >27 years. Further studies using a longitudinal design are needed to explore the associations of ethnicity-related decline of SM with health risks. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc.