Since various agents used in cancer chemotherapy exhibit antimicrobial activity in vitro, we performed sequential quantitative cultures of saline gargles obtained from patients receiving cancer chemotherapy to determine if such chemotherapy alters the composition of the aerobic oropharyngeal flora. When we compared results of cultures obtained from 12 patients just before and at various times after receiving courses of cancer chemotherapy, we observed small, though significant reductions in the numbers of total bacteria, alpha-hemolytic streptococci and inhibitory streptococci two to seven days after courses of chemotherapy. A concomitant increase in the percentage of patients colonized by gram-negative bacilli occurred. Of the chemotherapeutic agents used to treat our subjects, only doxorubicin exhibited antimicrobial activity in vitro. All four alpha-hemolytic streptococci, but none of the seven strains of gram-negative bacilli examined, were inhibited by doxorubicin at concentrations of less than or equal to 12.5 mg/l. Doxorubicin had a modest enhancing effect on in vitro adherence of gram-negative bacilli to human embryonic lung cells. These data suggest that cancer chemotherapy might play a role in colonization of cancer patients by gram-negative bacilli by creating a microbiologic vacuum conducive to such colonization. In this way, cancer chemotherapy might contribute to the high incidence of gram-negative bacillary pneumonia among patients with malignant neoplasms.