Fifty-eight episodes of catheter-related sepsis in 21 patients receiving home parenteral nutrition were retrospectively studied. Of 81 organisms isolated from the blood, 59% were Gram-positive cocci, 25% were Gram-negative bacilli, and 16% were yeast. Attempts to treat bacterial infections at home with antibiotic therapy while the catheter remained in place were made; fungal isolation resulted in immediate hospitalization and catheter removal. Gram-negative infections more often resulted in eventual hospitalization (92%) and catheter removal (50%) than Gram-positive infections (57% hospitalization and 23% catheter removal). Empiric therapy with 1 g of cefazolin intravenously every 12 hr was successful in only 33% of episodes caused by coagulase-negative staphylococci, whereas vancomycin was successful in 62%. Sensitivity testing was not a reliable guide for antibiotic choice for treatment of these infections. Cefazolin, 1 g, intravenously every 12 hr was successful in only 25% of Gram-negative episodes treated empirically with this regimen. We conclude that our home parenteral nutrition patients should be hospitalized for a few days upon presentation with a catheter infection for clinical evaluation and aggressive antibiotic therapy. Vancomycin is the preferred drug for treatment of catheter-related infections caused by coagulase-negative staphylococcus.