One local side-effect closely related to the use of parenteral fluoroquinolones is phlebitis. The occurrence of this phenomenon is largely thought due to the damage of endothelial cells with subsequent inflammation. In order to evaluate the effect of ciprofloxacin, fleroxacin, and ofloxacin on the viability of human umbilical venous endothelial cells (HUVEC), intracellular ATP levels were measured by a luciferin-luciferase assay. Prostacyclin (PGI2) and thromboxane A2 (TXA2) were determined by means of direct radioimmunoassay. Commercially available preparations of ciprofloxacin (2 mg/ml) and fleroxacin (4 mg/ml) reduced the intracellular ATP content by 75.9 +/- 1.9% and 82.1 +/- 0.6%, respectively, within 20 minutes, indicating severe damage of endothelial cells. Incubation with ofloxacin (2 mg/ml) did not have any detrimental effect. All fluoroquinolones were tolerated well by endothelial cells at low concentrations up to 20 micrograms/ml. Concentrations between 100-200 micrograms/ml gradually led to functional alterations such as increased PGI2 release. The tolerance of intravenously applied antibiotics has been tested in animal models. Use of human venous endothelial cells for testing antibiotic solutions for intravenous application provides a valuable alternate model for tolerability.