The pH- and temperature-responsive poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAm/MAA) nanoparticles are of potential application in targeted drug delivery. Their responsive properties in the presence of human serum albumin were investigated using dynamic light scattering (DLS), protein assay, and electron spin resonance (ESR) spectroscopy. Their interaction with human monocytes and polymorphonuclear leukocytes (PMNLs) was studied using scanning electron microscopy (SEM) and oxygen consumption method. The nanoparticles exhibited a volume phase transition at 35-40 degrees C in Hanks balanced salt solution (HBSS) and in phosphate buffer solution (PBS) of pH 7.4. The diameter of the nanoparticles decreased slightly in the presence of HSA at 25 degrees C at neutral pH, whereas an increase in the diameter in pH 6 PBS at 40 degrees C was revealed. The amount of albumin adsorbed onto the nanoparticles decreased with increasing temperature. The ESR spectra of spin labeled HSA indicated a more restricted environment in the nanoparticles at elevated temperatures. The stimulation of PMNL oxygen consumption by PNIPAm based nanoparticles, an indication of phagocytosis of the particles, was not observed regardless whether the nanoparticles were incubated in plasma or serum. In contrast, the more hydrophobic polystyrene (PSt) particles induced a significant increase in the rate of oxygen consumption after the incubation. PNIPAm/MAA-grafted-PSt particles behaved similarly to the PNIPAm/MAA nanoparticles, suggesting that surface properties dictate the recognition of colloids by PMNLs.