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At our hospital (Jefferson Davis Hospital, Houston, Tex.) since 1979, non-group D alpha-hemolytic streptococci have been isolated with increasing frequency from neonatal blood cultures with clinical findings of sepsis. A total of 47 such isolates were identified to the species level by the scheme of Facklam and were compared with 57 genital isolates from 167 maternity patients. Among the genital isolates, S. sanguis II and S. MG-intermedius accounted for 53 and 28%, respectively, and both were significantly less common in neonatal cultures (23 and 11%, respectively; P less than 0.05). Among neonatal isolates, S. mitis was the single most frequent species (35%), in contrast to its rare occurrence in maternal cultures (3.4%; P less than 0.001). The disparity between the prevalence of S. mitis in neonatal compared with maternal cultures suggests that this species of non-group D alpha-hemolytic streptococci may have increased virulence in neonatal hosts.