A prospective study of neonatal sepsis conducted at the Institute of Maternal and Child Health, Calicut for a period of twelve months, from November, 1978 to October, 1979 revealed epidemic infection caused by Salmonella typhimurium resistant to multiple antibiotics. During this period 30 neonates developed septicemia due to this organism and it was isolated from blood, feces, cerebrospinal fluid, pus, and pericardial fluid. Salmonella tvphimurium sepsis was more in males (2:1), in preterms (2:1) and in asphyxiated babies. The commonest clinical signs were poor feeding (29), lethargy (28), acidosis (26), apnoea (19), jaundice (17), cyanosis (17), pallor (16) and respiratory distress (16). The commonest clinical picture was undifferentiated bacteremia (16). Diarrhea occurred in 8, meningitis in 5, and arthritis in one. Of seventeen babies with jaundice, 6 had hyperbilirubinemia. Of the 30 neonates only 7 of them survived. Of the different treatment schedules employed a combination of ampicillin, gentamicin and furazolidone was found most effective. All isolates were resistant to high levels of penicillin, chloramphenicol, streptomycin, tetracycline, ampicillin and kanamycin and were sensitive to gentamicin and furazolidone. The resistance was plasmid borne and could be transmitted to recipient Esch. coli K 12 in triparental cross with transfer factor donor.