In this study, an in vitro model has been developed to examine the interactions of macrophages with ultrahigh molecular-weight polyethylene (UHMWPE) and high-density polyethylene (HDPE) particles. Polyethylene particles are the major constituent of the material debris formed as a result of orthopedic implant wear. However, the study of polyethylene particle interactions with cells has been limited. UHMWPE (18-20 microns) and HDPE (4-10 microns) were suspended in soluble collagen type I and subsequently solidified on glass coverslips. The particle chemistry was characterized by Fourier transform infra-red spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). Mouse cell line macrophages (IC-21) were established on the collagen-particle substrata and maintained for up to 24 h. The response of the cells to the particles was examined by light and transmission electron microscopy (LM and TEM), as well as by scanning electron microscopy (SEM), and compared to cells on control collagen surfaces without particles. Histological analysis of the samples revealed that the macrophages surrounded larger particles (18-20 microns) and the cells appeared to be attached to the surface of the particles, and the smaller particles (4-10 microns) had been phagocytosed within 2 h. Inflammatory cytokines (TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6), lysosomal enzymes (beta-galactosidase and hexosaminidase), and prostaglandin E2 were released into the medium, and IL-1 alpha, IL-1 beta, PGE2, beta-galactosidase, and hexosaminidase levels were significantly increased over collagen control values. The results demonstrate active phagochemotaxis by macrophages for wear particulates and validate this model as a means of studying the specific in vitro interactions of polyethylene with cells.