The surface force interactions between individual 8 mu m diameter spheres and atomically flat substrates have been investigated using atomic force techniques. The lift-off force of glass, polystyrene, and tin particles from atomically smooth mica and highly oriented pyrolitic graphite substrates was determined as a function of the applied loading force in an inert nitrogen environment. While the relative magnitudes of the measured lift-off force were found to scale as expected between the various systems studied, the absolute values were a factor of similar to 50 smaller than expected from the Johnson, Kendall, and Roberts theory. The surface topography of representative spheres was characterized with atomic force microscopy, allowing a quantitative assessment of the role that surface roughness plays in the adhesion of micrometer-size particles to substrates. Taking into account the radius of curvature of the asperities measured from the atomic force scans, agreement between the measured and theoretical estimates for the lift-off forces was improved, with the corrected experimental forces about a factor of 3 smaller than theoretical expectations.