Previous studies have shown that lectin-induced human mononuclear leukocyte (MNL) proliferation was influenced by quinoline derivative antibiotics (quinolones), depending on both the dose and the antimicrobial agent used. Since the production of interleukin-2 (IL-2) is known to be involved in the proliferation of immune cells, we investigated the effects of three quinolones: ciprofloxacin (Cip), ofloxacin (Ofl) and pefloxacin (Pef) on IL-2 production in vitro by phytohemagglutinin (PHA)-stimulated human MNL. IL-2 activity in the supernatants of PHA-stimulated MNL was found to be enhanced by quinolones in a dose- and time-dependent manner. Increased IL-2 activity was observed using Cip, Ofl or Pef at therapeutically achievable blood concentrations (5-10 micrograms/ml). Since at these concentrations the PHA-induced proliferative response of MNL was not impaired by quinolones, the increased recovered IL-2 activity was not related to a decreased absorption of IL-2 by activated MNL. At high antibiotic concentrations (25 micrograms/ml), the enhanced IL-2 activity might be related (i) to increased accumulation resulting from the decreased proliferation induced by the quinolones at these concentrations, and (ii) to a true increased IL-2 production by the cells. In fact, an increased IL-2 recovery in presence of quinolones was always observed after blocking the cell cycle by mitomycin C, and was therefore independent of DNA-synthesis. Furthermore, the expression of IL-2 receptors was not modified by Cip, Ofl or Pef. These data show that quinolones increased IL-2 synthesis by MNL and suggest the potential usefulness of these antibiotics, not only as antimicrobial agents, but also as modulators of immune responses.