Surface roughness has been shown to affect differentiation and local factor production of MG63 osteoblast-like cells. This study examined whether surface roughness alters cellular response to circulating hormones such as 1 alpha,25-(OH)2D3. Unalloyed titanium (Ti) disks were pretreated with HF/HNO3 (PT) and then were machined and acid-etched (MA). Ti disks also were sandblasted (SB), sandblasted and acid etched (CA), or plasma sprayed with Ti particles (PS). The surfaces, from smoothest to roughest, were: PT, MA, CA, SB, and PS. MG63 cells were cultured to confluence on standard tissue culture polystyrene (plastic) or the Ti surfaces and then treated for 24 h with either 10(-8) M or 10(-7) M 1 alpha,25-(OH)2D3 or vehicle (control). Cellular response was measured by assaying cell number, cell layer alkaline phosphatase specific-activity, and the production of osteocalcin, latent (L) TGF beta, and PGE2. Alkaline phosphatase activity was affected by surface roughness; as the surface became rougher, the cells showed a significant increase in alkaline phosphatase activity. Addition of 1 alpha,25-(OH)2D3 to the cultures caused a dose-dependent stimulation of alkaline phosphatase activity that was synergistic with the effect caused by surface roughness alone. 1 alpha,25-(OH)2D3 also caused a synergistic increase in osteocalcin production as well as local factor (LTGF beta and PGE2) production on the rougher CA, SB, and PS surfaces, but it had no effect on the production on smooth surfaces. The inhibitory effect of surface roughness on cell number was not affected by 1 alpha,25-(OH)2D3 except on the SB surface. 1 alpha,25-(OH)2D3 decreased cell number, increased alkaline phosphatase activity and osteocalcin production, and had no effect on LTGF beta or PGE2 production by MG63 cells grown on tissue culture polystyrene. These data suggest that bone cell response to systemic hormones is modified by surface roughness and that surface roughness increases the responsiveness of MG63 cells to 1 alpha,25-(OH)2D3. They also suggest that the endocrine system is actively involved in normal bone healing around implants.