Bleach sputum concentration and fluorescence microscopy (FM) are reportedly more sensitive than direct Ziehl-Neelsen (ZN) sputum smears for tuberculosis detection, and might be particularly valuable for human immunodeficiency virus (HIV)-positive patients excreting fewer bacilli. This study, implemented in Yaoundé, Cameroon, determined the yield from both direct and bleach-concentrated FM and ZN duplicate smears against culture on Löwenstein-Jensen medium, with HIV testing from the sputa. From 418 HIV-positive and 518 HIV-negative tuberculosis suspects, 185 (44.3%) and 243 (46.9%) cultures, respectively, grew Mycobacterium tuberculosis. Direct ZN was positive for, respectively, 87 (47.0%) and 202 (83.1%) of the culture-positive cases. Proportional incremental yield over direct ZN from ZN and FM bleach smears was 14.9% (P < 10(-3)) and 17.2% (P < 10(-4)) for HIV-positive versus 4.9% (P < 10(-2)) and 2.0% (non-significant) for HIV-negative cases. There was no gain from direct FM. Bleach FM showed 2% excess false positives. The bleach concentration, therefore, increases the yield of ZN and FM, particularly from HIV-positive patients, but with a higher risk for false positives with bleach FM. With excellent baseline direct ZN, the gain remains modest. Field studies under real-life conditions are needed to determine whether it is worth the risks and operational challenges in HIV high-prevalence populations. FM was not more sensitive than ZN in this study, probably because of sub-optimal objective power and background staining. Culture on solid media with sparing laurylsulfate decontamination was clearly superior for HIV-positives, but it remains to be seen if culture also leads to more cases started on treatment routinely.