The impact of increased macrolide consumption on the resistance of common respiratory pathogens to erythromycin and azithromycin was evaluated. The study focused mainly on azithromycin. During the period from 1991 to 1996, a 3.5-fold increase in macrolide prescriptions for outpatients was observed in Slovenia. Compared to 1994, when no macrolide resistance was evident in Streptococcus pyogenes and noninvasive Streptococcus pneumoniae, a significant increase in macrolide resistance was observed in these two pathogens in 1997. Moraxella catarrhalis remained uniformly susceptible to macrolides. Close monitoring of macrolide resistance of common respiratory pathogens is thus necessary.