Standardized extracts of Echinacea, cat's claw, and saw palmetto were each evaluated for ability to activate macrophage and natural killer cells, in vitro, using two independent measures of activation for each immune cell population. A standard series of exposure concentrations were tested for each herbal extract in a panel of four assays that evaluated macrophage phagocytosis, macrophage synthesis of interleukin-12, natural killer (NK) cell cytocidal activity (synthesis of granzyme B), and NK cell synthesis of interferon-gamma. Macrophage phagocytosis was stimulated by all three herbs tested: saw palmetto (up to 2.3-fold, P < .05), Echinacea (up to 3.6-fold, P < .01), and cat's claw (up to 4.7-fold, P < .01). Additionally, NK cell synthesis of interferon-gamma was stimulated by saw palmetto (up to 6.3-fold, P < .01) and Echinacea (up to 8.1 fold, P < .01) but not by exposure to cat's claw. None of the three herbs stimulated macrophage synthesis of interleukin-12 or NK cell synthesis of granzyme B. Comparison of the in vitro data with our earlier observations that cat's claw and Echinacea (but not saw palmetto) were each effective in reducing B16/F10 lung tumor colony formation in C57BL/6J mice suggests macrophage activation is the primary means by which these herbs modulate the immune system. Thus, macrophage activation (phagocytosis) may provide a potentially higher throughput method to identify herbal extracts with in vivo stimulatory effects.