Profiles of the invasion and intracellular growth of M. tuberculosis (MTB) and M. avium complex (MAC), which had been adapted to intramacrophagic environment, within Mono Mac 6 human macrophages (MM6-M phi s) and A-549 human type II alveolar epithelial cells (A-549 cells) were studied. In this study, we used the organisms grown in MM6-M phi s (intracellularly-adapted: I-type) and those passaged in 7H9 liquid medium (extracellularly-adapted: E-type). First, I-type MTB was less efficient than E-type MTB in invading into MM6-M phi s, while I-type MTB invasion into A-549 cells was greater than of E-type MTB. On the other hand, I-type MAC was more efficient than E-type MAC in entering both into MM6-M phi s and A-549 cells. Second, the ability of MTB and MAC to replicate within MM6-M phi s was increased by intracellular passage of these organisms through MM6-M phi s. In contrast, the ability of these organisms to grow within A-549 cells was decreased to some extent by intramacrophagic passage. These findings suggest that growth within M phi s changes the efficiency of MTB and MAC in invading and replicating in M phi s and type II alveolar epithelial cells.