Routinely changing the intravenous delivery system (fluid containers and administration set) every 24 h is widely practiced in American hospitals to reduce the risk of septicemia caused by contaminated infusate. We did a prospective clinical study to ascertain whether changing at longer intervals could be justified. At the conclusion of infusion therapy through one system, both the cannula and an aliquot of remaining fluid were cultured quantitatively. Of 790 infusions, contaminated infusate was detected in one (0.39%) of 258 discontinued and sampled after 1 to 24 h of continuous use, three (0.84%) of 359 after 25 to 48 h, and one (0.58%) of 173 after 49 to 71 h; none of these five contaminated systems produced septicemia. However, five cannula-related septicemias were identified during the study, none associated with concordant contamination of infusate. Routinely replacing the delivery system every 48 h seems to be justified and could result in considerable savings to hospitals. Infection of the cannula wound and contamination of infusate seem to be unrelated.