Surface roughness affects proliferation, differentiation (alkaline phosphatase and osteocalcin), local factor production [transforming growth factor (TGF) and prostaglandin E 2 (PGE 2 )], and response to 1,25-(OH) 2 D 3 (1,25) of MG63 osteoblast-like cells. In this study, we examined whether the effect of surface roughness on MG63 cells is mediated by prostaglandins produced by the cells. Unalloyed titanium (Ti) disks were pretreated with HF/HNO 3 (PT) and then machined and acid-etched (MA). Disks were also coarse grit-sandblasted (SB), coarse grit-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 the Ti disks in the presence or absence of 10 -7 M indomethacin (Indo), a specific inhibitor of cyclooxygenase activity, resulting in decreased prostaglandin production. When the cells reached confluence, cell number, cell layer alkaline phosphatase specific activity (ALPase), and osteocalcin (OC) and latent TGF (LTGF) production were determined. In addition, confluent cultures which had been grown in the absence of Indo were exposed to 10 -7 M 1,25, 10 -7 M Indo, or a combination of the two for 24 h. On the rougher surfaces, cell number was decreased and ALPase, OC, and LTGF were increased. When indomethacin was present throughout the culture period, the effect of surface roughness on cell number, OC, and LTGF was abolished. ALPase was reduced, but surface roughness-dependent effects were still observed. Addition of indomethacin to confluent cultures for 24 h had no effect on any of the parameters examined, with one exception: Cells cultured on MA surfaces exhibited a more differentiated phenotype. 1,25 increased all parameters examined on SB, CA, and PS surfaces. When indomethacin was added with 1,25, the 1,25dependent effects on cell number and OC and LTGF production were abolished; however, ALPase was unaffected. This indicates that bone cell response to systemic hormones may be modified by implant surface roughness. This effect may be mediated, at least in part, by prostaglandins produced by the same cells.