Catheter-related sepsis is a serious and common complication in patients receiving home parenteral nutrition (HPN). Prevention measures, prevalence of infections, types of agents and implanted central venous catheters (CVC), effectiveness of antibiotic therapy have been evaluated in 221 patients consecutively followed in our unit from January 1995 to December 2000. The clinical diagnosis of catheter-related infection was made using well-defined criteria. Patients were divided into two groups: A and B, receiving instructions with different modalities: standard (A) and detailed (B), respectively. Sixty CVC-related sepsis occurred in 32 (14%) patients. A multivariate analysis showed that the duration of HPN (P<0.001; OR=0.9), type of catheter (P=0.009; OR=0.12) and type of disease (P=0.033; OR=4.92) significantly influence catheter infection. The type of implanted CVC (159 port-a-cath in 153 patients and 71 tunnelled in 68) seems to affect the infection rate, this being lower in tunnelled (P=0.03). Infection rate was lower in B vs A group (P<0.001) with all types of catheters, suggesting the preventive role of very careful training. In particular, the incidence of CVC-related sepsis was 6/1000 days of HPN (i.e. 6/1000 days of catheterization) in Group A and 3/1000 in Group B. Systemic and antibiotic lock therapy was performed with an 83% successful rate. Gram-positive bacteria were the most frequent CVC infection agents, which are usually eradicated by antibiotic therapy lasting 7 days.