Bone loss is a significant clinical problem, and treatments utilizing donated graft material are limited. To meet future demands in the healthcare industry, there has been a shift of outlook toward the use of bioactive materials for tissue regeneration. A number of in vivo and in vitro studies have highlighted the potential of the bioactive glass ceramic 45S5 Bioglass as a synthetic regenerative scaffold. The application of sol-gel processing techniques has led to the synthesis of mesoporous bioactive glasses with greater textural and compositional variety. In this study, we evaluated the effects of supplemented tissue culture medium containing up to 203 ppm silica prepared by static soaking of particles of 58S sol-gel bioactive glass (58% SiO(2), 33% CaO, 9% P(2)O(5)) on the in vitro proliferation and differentiation of murine and human primary osteoblasts. These extracts had a higher silica content than those used previously in studies of 45S5 Bioglass, because of the faster rates of ion exchange permitted by the higher surface area-to-volume ratio of mesoporous glass. We found that osteoblasts from both species increased their proliferation in response to the glass-conditioned medium. In addition, the extent to which supplemented medium could alter cell differentiation varied with time in culture. Proliferation induced by supplemented medium paralleled effects induced by treatment with basic fibroblast growth factor, a known mitogenic growth factor for osteoblasts. Bone nodule formation was also increased by exposure to the glass-conditioned medium and this effect was positively correlated with the dose of glass used to prepare the medium. Apoptosis was stimulated by glass-conditioned medium in murine osteoblasts, but inhibited in human osteoblasts. These data demonstrate the bioactive effects of dissolution products derived from sol-gel materials on primary osteoblasts and complements in vivo studies that indicate the suitability of this material as a bone graft substitute.