An epidemiologic survey of antibiotic resistance among pneumococcal isolates collected during 1988 and 1989 in Hungary indicated that as many as 58% of all isolates and 70% of isolates from children were resistant to penicillin. These figures surpass even the highest values reported thus far for Spain and South Africa for the same period. Almost or more than 70% of the penicillin-resistant isolates were also resistant to tetracycline, erythromycin, and cotrimoxazole and approximately 30% to chloramphenicol. Intravenous administration of ampicillin (30 mg/kg) did not interfere with the growth in the cerebrospinal fluid of three resistant strains introduced into the rabbit model of experimental meningitis. No resistant strain showed beta-lactamase activity. A representative highly resistant strain contained altered penicillin-binding proteins (low penicillin affinities and abnormal molecular sizes) and was also resistant to the lytic and killing effects of penicillin.