The effects of two macrolides which are known to accumulate in macrophages, namely azithromycin (AZM) and erythromycin (ERM), on in vitro nitric oxide (NO) synthesis by lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages were examined. AZM and ERM were added to peritoneal macrophage cultures (1 x 10(5) adherent cell/well) at concentrations 0.5, 10 and 50 mu g/ml, 1 and 4 days prior to LPS stimulation, NO response was measured by nitrite production. When compared to the control wells, nitrite accumulation after LPS stimulation (1 mu g/ml) decreased by 39.8% (p<0.05), 6.5% (p>0.05), 3.5% (p>0.05) in the presence of 50, 10 and 0.5 mu g/mls of AZM, respectively. ERM decreased nitrite accumulation only minimally. Our results indicate that, in this murine peritoneal macrophage model, azithromycin but not erythromycin can alter NO response significantly.