The effect of methotrexate (MTX) and doxorubicin on the growth, metabolism and ultrastructure of Streptococcus mutans and Streptococcus sanguis was studied in vitro. Both anticancer drugs exerted an inhibitory effect on the oral streptococci. MTX was more inhibitory than doxorubicin. The minimum inhibitory concentrations (MICs) of MTX to S. mutans were 0.25-2.5 micrograms/ml and that of doxorubicin 0.2 mg/ml. The MICs of MTX and doxorubicin to S. sanguis were 0.025 micrograms/ml and 2.0-0.02 mg/ml, respectively. When saliva samples of patients with malignant tumors receiving various doses of MTX were analyzed, MTX was found to be secreted into the oral cavity at concentrations ranging from 0.014 to 4.486 micrograms/ml. The saliva of these patients was also found to inhibit the growth of S. mutans, and the inhibition zones were in accordance with the MIC values observed. The results suggest that anticancer therapy must be taken into account when the salivary microbiological findings of cancer patients are interpreted.