Preliminary evidence (n = 15) with semiquantitative (latex) determinations of C-reactive protein (CRP) suggested an unreliable CRP response in systemic Group B streptococcal infection. Recent experience with sequential, quantitative determinations of CRP in 10 infants surviving GBS infection documents that CRP can rise rapidly with systemic infection and fall rapidly with appropriate treatment. One infant with asymptomatic bacteremia had no increase in CRP, but in nine others with sepsis and/or meningitis the peak concentrations were from 4.2 to 31.9 mg/dl. Duration of elevated CRP ranged from 2 days in benign illness to 17 days in severe meningitis. Two infants with neurologic sequelae had concentrations greater than 20 mg/dl. Leukopenia, neutropenia and elevated immature neutrophil:total neutrophil ratio were frequently observed at the onset of infection. Leukocyte counts may be most helpful in making an early diagnosis, whereas CRP concentrations may document response, influence duration of antibiotic therapy and provide prognostic information.