This study describes a novel method which could be developed into a test system of evaluating the efficacy of antileprosy drugs. The method estimates incorporation of [14C]acetate into lipids of Mycobacterium leprae maintained within the 33B Schwannoma cell line. Schwannoma cell-resident M. leprae cells incorporated significant levels of radiolabel within their lipids during 12 days of incubation in vitro. This incorporation was markedly reduced by 5 micrograms of rifampin per ml (decrease, 81.62%); this decrease was observed within 24 h of addition of the drug. Dapsone also reduced the radiolabel incorporation into the lipids, but to a lesser extent (decrease, 27.58%). This system was also able to differentiate between rifampin-sensitive and -resistant strains of mycobacteria. It is suggested that since the effect of bacteriostatic (dapsone) and bactericidal (rifampin) drugs could be detected by using this technique, it may prove useful in screening novel drugs acting against M. leprae.