An evaluation was made as to whether freshly ground silica (14808607) was more surface reactive and/or cytotoxic than aged silica. The surface features of freshly fractured silica were different from those of aged silica. Respirable size freshly ground silica contained silicon based radicals that react with aqueous environments to produce hydroxide radicals. The free radical concentration and the biologic reactivity of freshly ground silica were higher than those of aged silica as measured by electron spin resonance (ESR) techniques and silica induced oxygen radical and hydrogen-peroxide release from Sprague-Dawley-rat alveolar macrophages and by lipid peroxidation. Freshly ground silica exhibited a greater cytotoxic effect on cellular membrane integrity producing a 1.5 fold increase in lactate-dehydrogenase release from macrophages, a 36 fold increase in hemolytic activity, and a three fold increase in the ability to induce lipid peroxidation. The authors propose that silicon based radicals on silica and the resultant generation of hydroxide radicals may be important in cell membrane damage by initiation of lipid peroxidation through a chain reaction. This mechanism may be particularly important in the pathogenesis of acute silicosis where inhalation of fresh silica occurs, as in sandblasting, rock drilling, tunnelling, and silica flour mill operations.