The objective of these studies was to investigate genes of importance in the pathogenesis of Aspergillus infections. To do so, we employed microarray methodology to explore gene expression in human monocytes infected with Aspergillus conidia as compared with unstimulated monocytes and those stimulated with lipopolysaccharide (LPS) signaling through TOLL-like receptor 4 (TLR4). We found 997 (P<or=0.05) differentially expressed (DE) genes in monocytes stimulated with conidia from Aspergillus fumigatus and 4976 (P<or=0.05) DE genes in monocytes stimulated with LPS. A total of 454 genes were only regulated by A. fumigatus stimulation. Selected genes were verified with qRT-PCR. Our study revealed significant changes in the expression of a number of genes of potential importance in the interaction between Aspergillus conidia and monocytes, including immune response genes and genes involved in apoptosis and initiation of Th1 response. Several of these changes in gene expression were unique to Aspergillus conidia and were not seen with LPS stimulation. These results do not support a role for TLR4 in the response to conidia. Further studies of genes regulated only by Aspergillus conidia may be of interest in the exploration of the pathogenesis of Aspergillus infections in man.