The purpose of the present study was to investigate expression of endothelial and inducible nitric oxide synthase in the MCF-7 human breast cancer cell line compared to a multidrug resistant variant, MCF-7-ADR. Immunohistochemical investigations demonstrated 51% of MCF-7 cells stained positive for endothelial nitric oxide synthase, with 46% positive for inducible nitric oxide synthase. However, in the breast cancer cell line that was multidrug resistant there was a much lower positive staining for endothelial nitric oxide synthase at 20% and for inducible nitric oxide synthase at 15%. For the multidrug resistant variant, there was also lower nitric oxide production and the band intensity for immunoblotting for endothelial nitric oxide synthase was weaker than for the parent cell line. These results lend further support to the proposal that expression of NOS is negatively associated with human breast cancer progression.