OBJECTIVES: To characterize the relationship between muscle mass and muscle strength in the US elderly population, and examine potential sources of population heterogeneity. METHODS: This study included individuals aged 50 and above from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 databases. Distributions of muscle mass measured via the height-adjusted appendicular skeleton muscle mass (aASM, in kg/m²), and muscle strength via the isokinetic quadriceps strength (IQS, in Newtons) were examined, stratified by age and gender.  The relationship between muscle mass (aASM) and muscle strength (IQS) was summarized using the partial correlation coefficient adjusting for age and gender.  The effects of individual comorbid medical conditions and body mass index (BMI) on the relationship between muscle mass and muscle strength were assessed using a series of multivariable regression models, using survey strata and weighting, with aASM, age, gender, and each variable of interest (e.g., diabetes) predicting muscle strength; and with an interaction between aASM and the variable of interest included to assess for effect modification. RESULTS: The study included 5139 individuals with a mean age of 66.2 years and 50.2% female.  Mean (SE) aASM was 7.2 (0.03) and declined with age, from 7.6 (0.05) for 50-54 year olds to 6.4 (0.04) for those 80 and older.  Mean (SE) IQS was 362.3 (2.8), declining from 426.6 (6.7) for 50-54 year olds to 241.6 (6.5) for those 80 and older.  aASM and IQS were positively correlated (partial correlation coefficient=0.365, p<0.0001).  Interactions between ASM and several factors (e.g., diabetes, arthritis and BMI) were statistically significant (P<0.05). CONCLUSIONS: Among individuals aged 50 and above in the United States, muscle mass and muscle strength are positively correlated.  BMI and certain comorbid medical conditions (e.g., diabetes and arthritis) appear to modify the effect of muscle mass on muscle strength.