An in vitro method to gauge metabolic heat response of macrophages (MØ) to particulates is described. Whereas the majority of work cited relies on chemical analysis to assess MØ response to particles, we have used isothermal microcalorimetry (IMC) for direct continuous measurement of metabolic heat production to gauge the response. IMC is a screening method, in that it ensures that no energy-consuming phagocytic response goes undetected, and that the aggregate metabolic magnitude of the responses is determined. A four-well IMC was used in all microcalorimetric measurements. To accommodate "zero-time" monitoring of the interaction of particles and cells, a set of identical test chambers was constructed for use in the IMC. MØs were injected from outside the IMC onto particles contained in collagen or gelatin on glass coverslips at the bottom of each chamber. IMC runs were performed using MØs only, MØs and lipopolysaccharide (LPS) positive control, and MØs and clean or LPS-bound particles of either high-density polyethylene (HDPE) or cobalt-chrome alloy (CoCr). Total heat produced by the negative controls (MØs alone) was lower than for MØ exposure to LPS or particles. The trend was a higher response for LPS-bound HDPE compared with clean HDPE particles, though not significant. In conclusion, our results have shown that IMC can be used to detect the heat associated with the phagocytosis of particulate materials by MØs in vitro.