The effect of bezafibrate (BZF) and clofibrate (CF), two therapeutic drugs displaying anticoagulant and antihyperlipoproteinemic activities, on the EPR-spectroscopic properties of ferrous nitrosylated heme–human serum albumin (HSA–heme–NO) has been investigated. In the absence of BZF and CF, HSA–heme–NO is a five-coordinate heme–iron system, characterised by an X-band EPR spectrum with a three-line splitting in the high magnetic field region. Addition of BZF and CF to HSA–heme–NO induced the transition towards a six-coordinate heme–iron species characterised by an X-band EPR spectrum with an axial geometry. These data indicate that HSA–heme–NO is a five-coordinate heme–iron system, BZF and CF acting as allosteric effectors, and show that the primary heme binding site and the CF cleft of HSA are conformationally-linked, regardless of their different location.