Antibiotic use in The Netherlands during the period 1994–1999 is described in relation to the resistance of routine isolates of Streptococcus pneumoniae . The average antibiotic use in the study period was 3.4 defined daily doses per 1000 persons per day (DDD/1000/day) pencillins, 0.066 DDD/1000/day β-lactams other than penicillins, 2.3 DDD/1000/day tetracyclines and 0.71 DDD/1000/day trimethoprim and sulphonamides, without apparent rise or decline. In contrast, the use of macrolides doubled from 0.51 DDD/1000/day in 1994 to 1.0 DDD/1000/day in 1997 and stayed at 1.07 DDD/1000/day in 1998 and 1999. In 1994 the first pneumococci isolated from patients showed 0.7% resistance to penicillin (intermediate plus full resistance), 2.5% to erythromycin, 4.2% to co-trimoxazole and 4.7% to tetracycline. In 1999 first isolates showed 1.5% resistance to penicillin, 3.8% to erythromycin, 4.4% to co-trimoxazole and 6.6% to tetracycline. The modest but significant rise in the resistance to erythromycin may have been caused by the increased use of macrolides in the years 1994–1997. The rise in resistance to penicillin seemed not to be related to increased β-lactam use.