We examined the in vitro effect of clarithromycin and azithromycin on cytokine production by LPS and Pansorbin stimulated human monocytes. At concentrations that are physiologically achievable, both antibiotics affected in vitro production of IL-1alpha, IL-1beta, IL-6, IL-10, GM-CSF and TNF-alpha to varying degrees. Of those individuals in whom a significant increase or decrease in cytokine production was noted, clarithromycin treatment resulted in a significant suppression of production of each cytokine in 71% and a significant increase in 29% of the individuals. Similar results were noted with azithromycin. The results with IL-6 and TNF-alpha in the clarithromycin studies were most striking. A significant decrease was noted in 60% of individuals for IL-6 and 86% for TNF-alpha. For azithromycin, the most interesting results were for IL-1alpha (decrease in 100% of individuals) and for TNF-alpha (decrease in 100% of individuals). These results show that both clarithromycin and azithromycin alter cytokine production in human monocytes and thus possess immunomodulatory activity.