Feeding and food choice are crucial to the survival of an animal. The nematode Caenorhabditis elegans feeds on various microorganisms in nature, and is usually fed Escherichia coli in the laboratory. To elucidate the mechanisms of food/non-food discrimination in C. elegans, we examined the accumulation of various fluorescent polystyrene microspheres in the absence and presence of bacterial food. In the absence of food and on agar plates, C. elegans worms actively accumulated 0.5 and 1 μm diameter microspheres, whereas those microspheres <0.5 μm or >3 μm were rarely accumulated. Carboxylate microspheres were accumulated more than sulfate or amine microspheres. These results of accumulation in the absence of food probably well simulate uptake of or feeding on the microspheres. Presence of food bacteria even at bacteria:nematode ratios of 1:100 or 1:10 significantly reduced accumulation of 0.5 μm microspheres, and accumulation was reduced to approximately one-fourth of that observed in the absence of bacteria at a ratio of 1:1. When accumulation of microspheres was examined with the chemical sense mutants che-2, tax-2, odr-1 and odr-2, or the feeding mutant eat-1, all the mutants showed less accumulation than the wild type in the absence of food. In the presence of food, the che-2 mutant showed more accumulation than the wild type. It is possible that C. elegans discriminates food both physically, based on size, and chemically, based on taste and olfaction.