Phorbol myristate acetate (PMA), a potent inflammatory agent with tumor-promoting activity, was examined for its effect on the growth of Mycobacterium lepraemurium (MLM) in the left hind footpad of mice. When the animals were infected with 10(4) MLM and received multiple injections of 3 micrograms of PMA in the infection site weekly during the first 2 months and biweekly thereafter, the growth of the bacilli was markedly enhanced. PMA injection in the infection site resulted in severe footpad swelling accompanied by inflammatory signs such as redness, edema, induration, and sometimes ulcer. Acetic acid, as potent an inflammatory and hyperplastic agent as PMA but without any appreciable tumor-promoting action, did not stimulate MLM growth when it was injected biweekly in the site of infection with MLM at a dose of 30 mumol per injection. When mice were infected with 10(8) MLM, proper elimination of bacilli from the infection site was observed during the first 3 months. In this case, multiple injections of PMA in the infection site resulted in the enhancement of the elimination of MLM by host defense mechanisms, although PMA caused as severe inflammation as that observed when MLM infection was produced with a small inoculum (10(4) MLM). In both cases, dexamethasone was synergistic with, but indomethacin and L-l-tosylamide-2-phenyl-ethylchloromethyl ketone were antagonistic to, the effect of PMA.