Actinomycotic mycetomas usually respond slowly to treatment with antibiotics. In an attempt to hasten clinical resolution, we used a 2-step regimen consisting of an intensive phase of therapy with penicillin, gentamycin and co-trimoxazole for 5-7 weeks, followed by maintenance therapy with amoxicillin and co-trimoxazole. Seven patients were treated, all of whom showed significant reduction in discharge and swelling after the intensive phase. Maintenance therapy was continued for 2-5 months after the lesions became completely inactive. Five patients completed maintenance therapy, which was given for 6-16 months (mean 10.7 months), and remained free of disease during a mean post-treatment follow-up period of 6.4 months. The other 2 patients also responded satisfactorily and continue to receive maintenance therapy. Side-effects necessitating a modification of the treatment schedule occurred in 2 patients but reversed on discontinuation of the drugs responsible. This treatment schedule produces a rapid clinical response during the initial, intensive phase and promotes compliance with the longer maintenance phase of treatment necessary to achieve a complete cure.