Streptococcus pneumoniae isolates relatively (0.1 microgram/mL < minimum inhibitory concentration < or = 1.0 microgram/mL) resistant to penicillin (RRP) have been recovered worldwide, but reports of therapy and outcome of systemic infections due to these strains are limited. This retrospective study of prospectively identified patients reviews the clinical features, management, and outcome of 19 children with systemic infections due to S pneumoniae. From January 1, 1989 to December 31, 1991, 13 of 244 blood (5.3%) and 4 of 32 cerebrospinal fluid (12.5%) pneumococcal isolates were relatively resistant to penicillin. The serotypes were as follows: 14 (12 isolates), 6 (4 isolates), 19 (2 isolates), 23 (1 isolates). One peritoneal fluid isolate and one joint fluid isolate were also relatively resistant to penicillin. The mean age of the 19 patients was 30 months (range 5 to 104 months), and five children had underlying disorders. Eleven children (nine inpatients) were treated initially with a parenteral cephalosporin. Six patients were treated as outpatients, and all had (occult) bacteremia. Three of these patients received ceftriaxone intramuscularly in the emergency department; five were treated with amoxicillin/clavulanic acid, and one received amoxicillin. Seven of 13 children treated in the hospital became afebrile in 48 hours. Three others were afebrile from the time of admission. Repeat blood cultures obtained within 24 to 48 hours after therapy was initiated were sterile in 10 children. All but one child responded to initial therapy. The recovery of S pneumoniae isolates relatively resistant to penicillin has increased in our hospital during the last 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)