In cases of advanced infection with human immunodeficiency virus, mycobacterial blood cultures are frequently used to diagnose disseminated infection with the Mycobacterium avium complex (MAC). However, no prospectively validated guidelines exist for the use of such cultures. In this study, a two-part model for predicting MAC bacteremia was developed and then validated prospectively. First, a CD4+ cell count of < or = 50/microL was used to predict bacteremia. Then, among patients with < or = 50 CD4+ cells/microL, the documentation of fever on more than 30 days during the preceding 3 months, a hematocrit of < 30%, or a serum albumin concentration of < 3.0 g/dL was used to predict bacteremia. This model had a sensitivity of 89% and positive and negative predictive values of 30% and 98%, respectively, for the identification of patients with bacteremia. Had the model been applied to patients in this study, the number of blood cultures performed would have decreased by 61%, but 11% of the positive cultures would have been missed. In short, this model can predict MAC bacteremia and can potentially guide the use of mycobacterial blood cultures.