The correlation between increased macrolide consumption and the resistance of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to macrolides in Slovenia from 1994 to 1999 was evaluated. The outpatient consumption of macrolides increased from 1.89 to 3.84 defined daily doses (DDD)/1000 inhabitants/day during the observation period. This increase in macrolide consumption was paralleled by a steady increase in macrolide resistance in S. pyogenes (from 0 to 7.4%, r = 0.90, P = 0.014) and upper respiratory S. pneumoniae isolates (from 0 to 9%, r = 0.82, P = 0.044). In other pathogens studied, no significant increase was detected.