Liver biopsy (LB) has been advocated for the detection of mycobacterial infections in patients infected with human immunodeficiency virus (HIV). To determine the effect of the use of this procedure on survival, we compared it terms of yield with histological findings and noninvasive microbiological procedures. We reviewed the cases of 98 patients who underwent 106 LBs as part of the diagnostic screening for fever of unknown origin. LB revealed 17 cases of mycobacterial infection. For all but one patient, the results of at least one noninvasive procedure were positive. In 85 cases where infections were not diagnosed by LB, 17 had infections documented by other procedures. When all culture results are considered, the mean (+/- SD) incubation time to the first positive culture was 15 +/- 5 days, whereas the mean (+/- SD) incubation time to the first positive culture of an LB specimen was 28 +/- 9 days. The survival time was not significantly increased for patients who underwent LB and had positive Ziehl-Neelsen-stained smears; these patients survived a mean (+/- SD) of 12 +/- 11 months, whereas patients with negative smears survived a mean (+/- SD) of 9 +/- 10 months. Noninvasive studies are preferable to LB for the diagnosis of mycobacterial infections in HIV-infected patients.