The in-vitro activity of clarithromycin, temafloxacin, and ethambutol were assessed by MIC, FIC and intra-macrophage killing determinations alone and in various combinations against ten pigmented and ten non-pigmented strains of Mycobacterium avium complex bacteria. Alone, either clarithromycin or temafloxacin were found to be active against M. avium, but the best results were obtained from combinations of drugs. Clarithromycin and temafloxacin together were found to have an additive effect against two of ten pigmented variants and one of ten non-pigmented variants. Clarithromycin and ethambutol demonstrated a synergistic effect against two pigmented and one non-pigmented strain, and an additive effect against five and three pigmented and non-pigmented strains, respectively. For temafloxacin and ethambutol, additive effects were observed in four and two pigmented and non-pigmented strains, respectively. In cultures of macrophages both clarithromycin and temafloxacin alone reduced the numbers of bacteria growing intracellularly after six days, but the most effective bactericidal combination was clarithromycin, temafloxacin, and ethambutol together.