Catheter-related sepsis is one of the major complications of total parenteral nutrition (TPN) therapy. The relationship between microbial colonization of the skin at the site of catheter insertion and colonization of the central venous catheter was investigated in 74 catheters used to administer TPN therapy in 53 patients. Semiquantitative culture specimens were obtained from the insertion site and intravascular and subcutaneous catheter segments at the time of catheter removal. Bacteria and/or fungi were recovered from 19 catheters and 19 insertion sites; of the 19 colonized catheters, 6 had sterile insertion sites. Organisms isolated from the remaining 13 catheters were isolated concurrently from the insertion site. Catheter-associated bacteremia or fungemia was observed in 10 of the 19 patients with colonized catheters. The association between colonization of catheters and the presence of more than 10(3) bacterial or fungal colony-forming units at the insertion site was significant (P less than 0.005). These results demonstrated that colonization of catheters by organisms present on the skin at the site of catheter insertion occurred twice as frequently as colonization by the hematogenous route. The results also suggested that colonization of catheters by organisms present at the insertion site occurred only after a threshold number of organisms was reached.