Fluoroquinolones can cause tendinitis and tendon rupture. However, toxicological as well as clinical information on quinolone-induced tendopathy is scarce. We performed extensive electron microscopic studies with Achilles tendon specimens from ofloxacin-treated rats. The drug was given at a dose of 1,200 mg/kg (body weight) orally. Juvenile Wistar rats received one or three oral doses each of 1,200 mg of ofloxacin/kg (body weight)/day. Three days after treatment, the tenocytes of their Achilles tendons showed degenerative alterations, such as multiple vacuoles and vesicles in the cytoplasm that had developed due to swellings and dilatations of cell organelles. Other indications of cell degradation were the occurrence of cell debris and cell detachment from the extracellular matrix accompanied by a loss of cell-matrix interaction. The tenocytes of juvenile Wistar rats that had been treated at day 36 with a single oral dose of 1,200 mg of ofloxacin/kg (body weight) and sacrificed either 3 or 6 months later exhibited similar degenerative alterations. The number of degenerative alterations of tenocytes after ofloxacin treatment was considerably higher in rats that had received a magnesium-deficient diet than in rats with normal magnesium status. Of the adult rats that had been treated once, 5 times, and 10 times with ofloxacin and killed 1 day later, only those with the 10-times treatment showed a significantly increased number of degeneratively altered tenocytes. In summary, effects observed in tendons show similar pathological features as described earlier in cartilage, indicating that quinolone-induced arthropathy and quinolone-induced tendopathy probably are different clinical manifestations of the same toxic effect on cellular components of connective tissue structures.Musculoskeletal adverse effects represent a small but significant fraction of the adverse effects observed during therapy with fluoroquinolones (0.5 to 2%). Besides arthralgia and myalgia, cases of tendinitis and tendon ruptures have also been described. As with quinolone-induced arthropathy, most cases of tendon disorders have occurred with pefloxacin. Tendinitis associated with other drugs such as ciprofloxacin, ofloxacin, norfloxacin, and enoxacin has been reported, but the incidence appears to be much lower. In trying to estimate the overall clinical significance of this effect, it should be kept in mind that probably quite a number of unidentified cases exist (2,3,22).Clinical information on quinolone-induced tendopathy is scarce. Selective clinical studies regarding this adverse effect have not been published, and toxicological data are very limited. Some studies in rats that have been published so far do not seem to reflect the clinical situation because the alterations are detectable in juvenile rats only and are preventable by dexamethasone (8-10).We performed extensive electron microscopic studies with Achilles tendon specimens from ofloxacin-treated rats. Our experiments were designed to answer several questions. First, are multiple do...