Azithromycin and erythromycin disk test results were compared to MIC values obtained in six different media. One hundred isolates were tested in triplicate, and geometric mean MICs were plotted against arithmetic mean zone diameters and regression statistics calculated. The test media evaluated did not markedly influence MIC values, but incubation in 5-7% CO2 resulted in a two- to four-fold decrease in the activity of both drugs. For testing Haemophilus influenzae and other species that need to be tested in 5-7% CO2, interpretive breakpoints for the macrolides and azalides should be modified to compensate for the anticipated decrease in activity.