Fluoroquinolone antibiotics such as ciprofloxacin can induce tendon pathology and have various effects on tendon-derived cells in culture. We are investigating whether ciprofloxacin modifies signalling responses in tendon cells. Human Achilles tendon-derived cells were preincubated with or without ciprofloxacin (50?µg/ml) and were then challenged with interleukin-1ß (IL-1ß, 1?ng/ml) for up to 48?h. Prostaglandin E2 (PGE2) output was assayed by ELISA. The expression of cyclooxygenase-2 (COX-2) was examined by Western blotting. IL-1ß stimulated a substantial and prolonged increase in the output of PGE2. Preincubation with ciprofloxacin reduced IL-1ß-induced PGE2 output at all times tested; the reduction at 48?h was 69% (99% confidence interval 59–79%; 15 experiments). Norfloxacin and ofloxacin also reduced PGE2 output. However, ciprofloxacin did not affect the induction of COX-2 by IL-1ß, measured at 4 or 48?h. Ciprofloxacin reduces IL-1ß-induced PGE2 output in tendon-derived cells. The reduction in PGE2 output could modulate various cellular activities of IL-1ß, and may be implicated in fluoroquinolone-induced tendinopathy.