An atomic force microscope (AFM) has been used to measure the force of interaction between individual biological microspheres (oocysts of Cryptosporidium parvum) and an amorphous silica surface (hydrolyzed AFM tip). One of the main barriers to oocyst contamination of drinking waters is provided by sand-bed filtration. The AFM tip has been functionalized to silica in order to investigate the interaction between oocysts and model sand (siliceous) particles at the most fundamental level. The AFM force curves have been compared and contrasted with the zeta-potentials of silica particles and oocysts obtained from electrophoretic mobility measurements. It has been concluded that there is a steric interaction between the silica surface and the oocyst material, in addition to electrical double-layer and van der Waals interaction. The proteinaceous materials on the surface of the oocysts are considered to be responsible for the steric interaction. The magnitude of the steric interaction is little changed by varying the pH and electrolyte concentration (i.e. changing the charge characteristics of surfaces has little effect on the magnitude of the interaction). Force curves suggest that once the silica and oocyst surfaces contact one another, protein-linked tethering can occur. Therefore, despite the large steric barrier, adhesion between oocysts and silica may occur. A measurement of the hardness of the Cryptosporidium oocyst surface has shown that the surface has silica-like hardness, which may explain why the oocysts are so resistant to disinfection. Finally, the effect on the surface force measurement of alignment between two curved surfaces has been reported. The findings have implications for all studies that force map surfaces that possess curvature.