Silver is commonly used as an antibacterial agent, e.g., in various medical applications, and the availability of silver nanoparticles (AgNP) has fueled this development. Their antibacterial properties are well defined, whereas there are concerns regarding unknown and potentially harmful effects of AgNPs on immune cells and an ongoing immune reaction. Aim of the present study is a comparison of the effects of AgNPs and ionic silver (Ag+) on cells of the innate immune system, in particular on neutrophil granulocytes and macrophages. The AgNPs were synthesized within hydroxylated polyester dendrimer templates via an in situ approach, generating five kinds of AgNPs with mean diameters from 2.0 to 34.7 nm.4 No impact is observed on phagocytosis and oxidative burst, as well as activation of the promoter for the pro-inflammatory cytokine TNF-alpha. In contrast, both AgNPs and Ag+, but not the dendrimer templates, trigger the release of neutrophil extracellular traps and inhibit the formation of nitric monoxide. On the molecular level, AgNPs and Ag+ cause elevated intracellular levels of reactive oxygen species and the second messenger Zn2+. Moreover, protein phosphatases are inhibited by an oxidative mechanism. Taken together, there are several effects of AgNPs on neutrophil granulocytes and macrophages in vitro, but these are not specific for AgNP, instead they are also observed with Ag+, and Ag+ released from AgNPs seems to be the component responsible for most of the particles' immunomodulatory activity.