The fluoroquinolone antibiotic ciprofloxacin (cipro) has been reported to upregulate interleukin 2 and interferon-γ production in lectin-stimulated lymphocytes. The aim of this study was to elucidate whether cipro and the immunosuppressive agent CsA have antagonistic action on cytokine synthesis. Accumulation of IL-2 and IFN-γ protein and mRNA were analyzed in polyclonally (PHA or Con A) or alloantigen-stimulated human peripheral blood lymphocytes. CsA added simultaneously with PHA partially blocked cytokine synthesis. The present study also shows that cipro supplemented with CsA and PHA resulted in significant higher concentrations of IL-2 (up to 60 times) and IFN-γ (4,3 times) as compared with PHA and CsA alone. Similar results were obtained with primary mixed lymphocyte reactions. In parallel, a greater amount of IL-2 and IFN-γ mRNA was observed in lymphocytes incubated with both cipro and CsA as compared with CsA alone. Our results reveal that CsA-dependent inhibition of both IL-2 and IFN-γ expression is counteracted by high concentrations of cipro. These findings may be of importance in clinical transplantation.