To evaluate the importance of protein adsorption and chemical composition of the solid surface on complement activation, we used mercaptoglycerol (MG) and mercaptopropionic acid (MPA) modified gold surfaces as model surfaces. The complement activation by these surfaces was determined by measuring fluid phase iC3b and C5b-9 in serum that had been in contact with the surfaces. In addition, "active" C3 deposition at the modified surfaces was measured with the use of ellipsometry, an optical technique. It was found that the MG surface caused pronounced productions of iC3b and C5b-9 in serum as well as increased C3 deposition on the surface. In contrast, the bare gold surface and the MPA surface caused very little complement activation. The MG surface seems to have a high affinity with immunoglobulin G (IgG) that may be one explanation for the high complement activation ability of the MG surface. However, complement activation at the MG surface was relatively insensitive to Mg-EGTA buffer at a high serum concentration, indicating alternative pathway activation when classical pathway activation was inhibited. Corresponding control experiments performed with Mg-EGTA serum at hydrophobic silicon surfaces precoated with IgG showed no sign of alternative pathway activation. At a lower serum concentration, classical pathway activation seemed to dominate at the MG surface and the hydrophobic silicon surface precoated with IgG. Most probably, it is the hydroxyl groups at the MG surface that are associated with alternative pathway activation.