Techniques to improve the sensitivity of smear microscopy would facilitate early tuberculosis (TB) diagnosis and disease control, especially in low-income countries where the positive predictive value is high. C 18 -carboxypropylbetaine (CB-18) is a zwitterionic detergent that helps to compensate for the innate buoyancy of mycobacteria, potentially enhancing recovery by centrifugation. Previous data suggest that CB-18 may increase the sensitivity of smear, culture, and molecular amplification diagnostic testing. The goal of the present study was to evaluate if the sensitivity of the smear technique using light microscopy could be improved by treating respiratory samples with CB-18. In the first phase, respiratory specimens were collected consecutively from patients with suspected pulmonary tuberculosis in a tertiary-care hospital in Rio de Janeiro, Brazil (236 specimens were analyzed). After protocol modifications, another 120 respiratory specimens were evaluated. The standard technique was N-acetyl-L-cysteine with sodium hydroxide (NALC-NaOH) treatment, smear concentration with centrifugation, and Ziehl-Neelsen staining. Culture on Löwenstein-Jensen slants was performed on all specimens for use as the "gold standard." No specimens from patients undergoing active TB treatment were included. The initial protocol for CB-18 processing resulted in a sensitivity of 59.6% and specificity of 96.8% compared to standard processing with a sensitivity of 66.0% and specificity of 96.8%. Using the modified protocol, the sensitivity of CB-18 increased to 71.4% with a specificity of 97.0% versus standard processing with a sensitivity of 61.9% and a specificity of 99.0%. The diagnostic yield of acid-fast bacillus smear with CB-18 in the absence of fluorescence microscopy and PCR compared to standard processing with NALC-NaOH was not significantly different, although the power to detect a difference by the modified assay was low.Tuberculosis (TB) remains one of the deadliest diseases worldwide, with an estimated 8.4 million new cases and over 2 million deaths each year (21). Smear microscopy is currently the most feasible microbiological method for diagnosis of pulmonary TB in developing countries due to its rapidity, low cost, and high positive predictive value for Mycobacterium tuberculosis (3). However, sputum smear microscopy with ZiehlNeelsen staining is only 60 to 70% sensitive for the diagnosis of pulmonary TB compared with sputum culture (2, 8). Among human immunodeficiency virus-infected persons the sensitivity of sputum Ziehl-Neelsen smears has been reported to be even lower (2, 6, 10). Delayed or missed diagnoses contribute to M. tuberculosis transmission and mortality due to TB (9, 11).Improvements in the sensitivity of smear microscopy would allow earlier diagnosis. TB programs could then optimize disease control from a public health standpoint as well as improve individual patient management (20). In previously published reports, homogenization and concentration of respiratory specimens by centrifugation have been ...