Review of the bacteriologic records of a large city-county hospital from 1970 through 1980 has indicated a substantial increase in the frequency of isolation of non-group D alpha-hemolytic streptococci from blood and cerebrospinal fluid of neonates since 1978. These organisms accounted for 23% of all cases of neonatal septicemia and meningitis in 1980, and as a group were exceeded only by group B streptococci (28%) in prevalence. Most neonates (91.2%) had early-onset infection (mean age = 1.4 days); approximately one-third were premature (less than 36 weeks' gestation). Maternal obstetrical complications were common. Nearly 80% of the infants had signs or symptoms suggesting bacterial sepsis. Findings such as concomitant meningitis, shock, chest roentgenogram abnormalities, leukopenia, abnormal numbers of immature neutrophils, and death were infrequent when compared to those accompanying other invasive neonatal bacterial infections, suggesting that non-group D alpha-hemolytic streptococci may be less virulent for the neonate or that neonatal host defense mechanisms are more effective in containing the infection. Careful surveillance for these potential neonatal pathogens seems warranted.