Selection and regrowth of variants resistant to 0.016-32 mg/L of rifampicin, which were present at a frequency of 10(-7) in the initial inoculum, were seen when large inocula (> 10(5) cfu/mL) of Staphylococcus epidermidis ATCC 35984 were incubated with the drug. Conventional MIC determinations using approximately 10(5) cfu/mL did not detect the resistant variants. Larger inocula increased the MIC by > 8000-fold. Population analysis showed that rifampicin concentrations above the MIC (measured at an inoculum of approximately 10(5) cfu/mL) select highly resistant variants (MIC > 256 mg/L) when large inocula (> or = 10(5) cfu/mL) were incubated with rifampicin. The resistant variants were stable through ten passages. It was not possible to prevent regrowth of the resistant variants by increasing the rifampicin concentration further. At subinhibitory concentrations there was no development of rifampicin resistance.