We studied 977 patients with culture-proved pulmonary tuberculosis retrospectively to determine the frequency with which patients were sputum smear negative but culture positive (S-C+) prior to treatment, the frequency with which patients developed the smear positive but culture negative (S+C-) status during treatment, and the implication of these 2 phenomena to the success of treatment. One fourth (25.6%) of the patients were repeatedly S-C+ prior to treatment; the frequency of this phenomenon was inversely proportional to the extent of disease and the presence of cavities. Patients who were S-C+ prior to treatment, and whose organisms were drug-sensitive, had the fastest sputum culture conversion rate. Patients who were S+C+ without far-advanced cavitary disease had a significantly slower conversion rate after 1 month of treatment, and those with far-advanced cavitary disease had the slowest conversion rate. Patients with drug-resistant organisms had slower conversion rates than did their counterparts with drug-sensitive organisms, but in all but 4 of these, sputum smears and cultures ultimately converted to negative. The S+C- phenomenon was observed in 20.4% of patients; its frequency was related to the extent of disease and to treatment regimens that contained rifampin. In all patients who exhibited the S+C- phenomenon, sputum smears converted to negative with continuation of the same treatment regimen.