The mass detection method and a method utilizing the electrochemical indicator methylene blue (MB) were used to study the interaction of human serum albumin (HSA) with thiolated 19-mer single stranded (ssDNA) or double stranded (dsDNA) DNA immobilized on a gold surface. We showed that HSA interacts both with ssDNA and dsDNA as is revealed from the shift of the reduction potential of the MB. The HSA presumably interacts with both the bases and sugar-phosphate backbone of ssDNA, while mostly with the sugar-phosphate backbone of dsDNA. The adsorption of HSA onto a layer composed of ssDNA on a gold support is non-specific and is described well by a Langmuir adsorption isotherm. The binding constant of HSA to ssDNA determined by the mass detection method using a quartz crystal microbalance (QCM) (K-c = 77.9 +/- 11.2 muM(-1)) was close to the value determined by electrospray mass spectrometry and electrophoresis, reported by other authors. (C) 2003 Elsevier B.V. All rights reserved.