Their unique mechanical and biological properties make polyurethanes (PUs) ideal materials for many implantable devices. However, uncertain long-term biostability in the human physiological environment limits their extensive clinical applications. Chronic inflammatory response associated with macrophage activation has been suggested as a prime factor; although the mechanism of macrophage activation in response to biomaterial surfaces and debris is still unknown. The overall objective of this work was to study the response of macrophages to PU materials in vitro by measuring cell viability and activity. The studies were carried out using phagocytozable-size PU particles from three types of commercially-available PUs: Pellethane 2363 80ABA (PL); Tecothane TT2065 (TC65); and Tecothane TT2085 (TC85). These polymers posess the same generic composition but differ in the length of hard and soft segments, as revealed by the FTIR and NMR studies. The results showed that PU particles affected both viability and activity of J774 macrophages. The percentage of mortality ranged from 1 to 15% with 10-100 microg ml(-1) of particles after 24 and 48 h incubation. These three types of particles induced different mortality on the macrophages. Specifically, the mortality with PL particles was 1-4% (p > 0.05), while the mortality with TC85 particles was 2-10% (p < 0.05) and 4-15% with TC65 (p < 0.05). Conversely, these particles also affected cell proliferation. Cell numbers increased by 132 and 167% after 24 and 48 h incubation, respectively, without particles, whereas the cell numbers increased only 46 and 78% with TC65, 66 and 105% with TC85, and 67 and 110% with PL in the presence of 100 microg ml(-1) of particles for the respective incubation times. PU particles also increased TNF-alpha release from macrophage. After having been incubated for 24 h with 100 microg ml(-1) particles of TC65, TC85, and PL, macrophages release TNF-alpha 7.4, 5.2, and 4.1 times more than the control. In conclusion, PU particles had cytotoxic effects on J774 macrophage at high concentrations. The order of macrophage response for three types of particles was TC65 > TC85 > PL. PU particles' effect on macrophage viability and activity depends on the concentration of particles and their chemical composition, especially on the ratio of hard to soft segments.