The acid-fast smear remains an important tool in the diagnosis of tuberculosis. Some reports have questioned the validity of this stain in situations of low prevalence. We examined the relationship between prevalence and predictive value of sputum smears in one laboratory during periods of both low and high laboratory prevalence of Mycobacterium tuberculosis. Smears were examined by fluorescence and confirmed by Kinyoun stain. The number of samples positive for mycobacteria increased from 128 (4.3%) of 2956 during the 1975 through 1978 study period to 197 (8.4%) of 2347 during the 1979 through 1982 study period. Of 47 positive smears during the first study period, only one was a false-positive. None of 96 positive smears during the second period was a false-positive. The positive predictive value of acid-fast microscopy was 97.9% and 100% for the two periods examined. We have demonstrated in practice the small effect of a shift in prevalence on the positive predictive value of an acid-fast smear when specificity is maintained.