The susceptibility patterns of group A streptococci over the last 6 years in our hospital were determined. Since our last study, carried out in 1987, all isolates have remained very susceptible in vitro to penicillin and all of the other (-lactam agents tested. We observed resistance to erythromycin, clindamycin, tetracycline, and ofloxacin. The prevalence of erythromycin-resistant group A streptococci did not change appreciably throughout the study period.Over the last few years there has been an increase in severe group A streptococcus (GAS) infections, including their suppurative and nonsuppurative sequelae (7,18). Penicillin remains the drug of choice for treatment of GAS infections, and ever since penicillin was first introduced all GAS strains have remained exquisitely sensitive to this antibiotic; despite this, failures of adequate penicillin therapy in the treatment of GAS pharyngitis are being described with increasing frequency (3,4,8).Erythromycin is currently recommended as an alternative antibiotic for treatment of GAS infections in patients allergic to penicillins or in cases of penicillin failure. While in vitro resistance to penicillin has not been described for GAS strains, resistance to erythromycin has been reported. Since 1959, when the first erythromycin-resistant GAS was described by Lowbury and Hurst (9), resistance to this antibiotic has been reported from several countries, with important variations in the resistance rates in different geographic areas; in 1979, Maruyama et al. (10) in Japan reported erythromycin resistance in 61.8% of GAS isolates, and in other parts of the world erythromycin-resistant GAS strains have occasionally been isolated, with resistance rates ranging from 0.7% (13) to 2 to 5% (1,5,6,16,19,20). In the last 5 years, an increased incidence has been reported from several centers (14,15,17,21).In 1987 we studied the susceptibility of 93 GAS isolates from clinical specimens to some commonly prescribed antibiotics (2) and reported the incidence of GAS strains resistant to erythromycin (3.3%), clindamycin (4.3%), and tetracycline (2.2%).The purpose of the present study was twofold: to ascertain whether the frequency of such resistant strains in our hospital had increased from 1987 to 1992 and also to determine the MICs of some of the newer oral antimicrobial agents against GAS.A total of 330 GAS strains isolated from clinical specimens between January 1988 and September 1992 in the Hospital Universitario San Carlos, Madrid, Spain, were studied, and the results were compared with those obtained with 93 strains isolated in 1987. Of the 330 GAS strains evaluated, we collected 80 in 1988, 74 in 1989, 76 in 1990, and 100 from * Corresponding author. January 1991 to September 1992. The sources of the isolates and sites of infection were the upper respiratory tract (75.7%), skin and subcutaneous tissues (8.8%), deep wound infections (8.5%), blood (4.2%), and miscellaneous (2.8%). The antibiotics tested in the previous study were penicillin, erythromycin, clindamycin, tetracy...