Depletion of body cell mass (BCM) in human immunodeficiency virus (HIV)-infected patients is strongly associated with disease progression and death. Although whole-body protein turnover is increased in HIV infection, it is not known whether protein intake is independently associated with BCM. The purpose of this study was to determine the associations, if any, between protein intake and several body composition variables in 467 weight-stable, HIV-infected men with CD4 <200 cells/mm(3) enrolled in a multicenter nutritional supplementation trial. Baseline BCM, total body fat and extracellular mass as measured by bioelectrical impedance analysis, dietary intake (24 h food recall) and muscle building activity assessed by structured interview were analyzed to determine association(s) between body composition variables and macronutrient intake. Multiple regression analysis showed that BCM was positively associated with body weight (P = 0.001), height (P < 0.001), protein intake (P < 0.001), muscle-building activity (P < 0.001) and African-American ethnicity (P < 0.05) and negatively associated with carbohydrate intake (P < 0.05), age (P < 0.001) and number of prior AIDS-related diagnoses (P < 0.001). We conclude that protein intake is associated with increased BCM, whereas carbohydrate intake is negatively associated with BCM in HIV-infected men, independently of muscle building activity.